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Adverse drug reactions ADRs are one of the major causes of morbidity and mortality worldwide. It is well-known that individual genetic make-up is one of the causative factors of ADRs. Approximately 14 million single nucleotide polymorphisms SNPs are distributed throughout the entire human genome and every patient has a distinct genetic make-up which influences their response to drug therapy. Cytochrome P 2B6 CYP2B6 is involved in the metabolism of antiretroviral, antimalarial, anticancer, and antidepressant drugs. These drug classes are commonly in use worldwide and face specific population variability in side effects and dosing. Parts of this variability may be caused by single nucleotide polymorphisms SNPs in the CYP2B6 gene that are associated with altered protein expression and catalytic function. Population variability in the CYP2B6 gene leads to changes in drug metabolism which may result in adverse drug reactions or therapeutic failure. So far more than 30 non-synonymous variants in CYP2B6 gene have been reported. The occurrence of these variants show intra and interpopulation variability, thus affecting drug efficacy at individual and population level. Differences in disease conditions and affordability of drug therapy further explain why some individuals or populations are more exposed to CYP2B6 pharmacogenomics associated ADRs than others. Variabilities in drug efficacy associated with the pharmacogenomics of CYP2B6 have been reported in various populations. The aim of this review is to highlight reports from various ethnicities that emphasize on the relationship between CYP2B6 pharmacogenomics variability and the occurrence of adverse drug reactions. In vitro and in vivo studies evaluating the catalytic activity of CYP2B6 variants using various substrates will also be discussed. While implementation of pharmacogenomic testing for personalized drug therapy has made big progress, less data on pharmacogenetics of drug safety has been gained in terms of CYP2B6 substrates. Therefore, reviewing the existing evidence on population variability in CYP2B6 and ADR risk profiles suggests that, in addition to other factors, the knowledge on pharmacogenomics of CYP2B6 in patient treatment may be useful for the development of personalized medicine with regards to genotype-based prescription. Adverse drug reactions ADRs are globally one of the major causes of morbidity and mortality Giardina et al. Drug clearance may vary up to fold between two individuals of the same weight taking the same drug dosage Stingl et al. This variation can be influenced by pathophysiological, physiological, or environmental factors. However, genetic polymorphisms in drug transporters, drug targets and most importantly drug metabolizing enzymes have been emphasized over the years as one of the major factors causing variability in drug response Weinshilboum, ; Evans and Relling, Variability in patient exposure and response to various medication have been associated to genetic variants in genes that code for CYP enzymes Lynch and Price, ; Zanger and Schwab, The human genome harbors 18 CYP families divided into 41 subfamilies encoding 57 genes. The CYP2B6 gene which consists of nine exons is located on chromosome 19 at position 19q It is highly expressed in the liver, and to a certain extent in the extrahepatic tissues such as brain, kidney, digestive tract and the lungs Lonsdale et al. These variants are referred as star alleles on the Pharmacogene Variation website with designated clinical function as normal, decrease, increase, no or uncertain function Thorn et al. Specifically, it is fully or partially involved in the catalytic biotransformation of at least 90 drugs. Table 1 shows selected drug substrates which are metabolism by CYP2B6. Interestingly, variability in the expression and function of the CYP2B6 enzyme alters the metabolism of these substrates leading to altered pharmacokinetics and therapeutic efficacy. Abnormal drug efficacy associated with patient CYP2B6 genotype has been reported in various populations Sarfo et al. Serious ADRs due to high-risk pharmacogenetic variants might be avoided by the use of preemptive genotyping Dolgin, ; Bielinski et al. The knowledge on pharmacogenomics of CYP2B6 in patient treatment may be useful for the development of personalized medicine with regards to genotype-based prescriptions. A significant interindividual variability in the mRNA expression, protein levels and activity of CYP2B6 has been reported in human liver microsomes Ekins et al. Developmental regulation age , gender and disease condition are other confounders of CYP2B6 differential expression and function Pearce et al. They also confer differences in the site of metabolism Lewis and Lake, Typically substrates of CYP2B6 are hydrophobic small molecules, neutral or weak bases, very lipophilic with one or two hydrogen-bond acceptors Ekins et al. Table 1 indicates that CYP2B6 catalyzes demethylation, hydroxylation and oxidation reactions to form active or inactive metabolites Hidestrand et al. It is predicted that CYP2B6 is the major catalytic enzyme in the biotransformation of important drugs commonly used worldwide. In combination with other cytochromes, CYP2B6 also plays a minor role in the metabolism of other xenobiotics. CYP2B6 variants are substrate specific in their metabolic function. Thus, evaluating the impact of each enzyme variant on the metabolism of a specific substrate is of clinical importance Ariyoshi et al. Wide variability in CYP2B6 allelic frequencies is reported across populations. Furthermore, allele frequency at the global level may not represent intraethnic differences within a specific population Table 2. Table 2. Selected studies revealing variability in allele frequency of CYP2B6 alleles in different ethnicities. Efavirenz EFV is classified as an effective non-nucleoside reverse transcriptase inhibitor used in the treatment of HIV infection 1 , 2. As part of the highly active antiretroviral therapy, EFV is used in combination with other nucleoside reverse transcriptase inhibitors NRTIs 1, 2. EFV, which is presented in the form of mg once daily or in a reduced dose of mg oral tablets, is metabolized mainly by hepatic CYP2B6. EFV therapy is limited due to its narrow therapeutic window, thus, there exist a small difference between therapeutic and toxic doses. ADRs which are linked to the use of EFV includes increased risk of neurotoxicity, neuropsychiatric disorders, sleep disorders, high cholesterol level and drug induced liver disease Cohen et al. Table 3. CYP2B6 polymorphisms and adverse drug reactions reported amongst patients in various ethnicities. Its usage is limited due to side effects including hepatotoxicity, fever, Steven-Johnson syndrome and toxic epidermal necrolysis Ciccacci et al. Studies suggest dose reduction in patients harboring CYP2B6 poor metabolizer variants Schipani et al. Some studies have examined the reasons for such disparity in the use of EFV. It was observed that countries with higher income had greater access to novel drugs and new drug classes as first-line treatment than countries with low income Gokengin et al. Although most HAART regimens are given free to patients in all countries, the high level of donor dependency in LMICs might be a major obstacle to accessibility to new, expensive, more quality and less toxic drugs Gokengin et al. The high cost of new first-line drugs with better tolerability and lower toxicity influences the choice of treatment regimen, with high income countries HICs choosing regimens that include new drugs compared to LMICs who depend on cheaper regimens Gokengin et al. This genomic diversity of African populations has been observed for many genes Rajman et al. DGT may be unsuitable for patients with hepatitis B and C infection due to elevated levels of hepatic enzyme Vitoria et al. Risk of hypersensitivity reactions and development of renal failure may be observed Vitoria et al. New-onset or worsening hepatic or renal toxicity with longer cumulative exposure is a potential risk Vitoria et al. In pregnancy, there are concerns that the baby may be harmed, thus women are recommended to take effective birth control while on the drug Vitoria et al. Therefore, long term use of DTG is still under concern Kouanfack et al. A recent communication in December by Siedner et al. Unfortunately, much care is not given to HIV patients who have comorbid conditions, thus increasing the risk of ADRs amongst these patients Labarga et al. For example, patients with liver disease and hepatitis may experience enhanced hepatotoxicity due to EFV Agbaji et al. Certain preexisting conditions, such as mild psychiatric disorder, may be exacerbated by EFV. As such individualized prescriptions taking into account the pharmacogenetic profile, patient vulnerability caused by comorbid disease, and the toxicity profile of the drug will help to reduce ADR amongst these group of individuals in any part of the world. Cyclophosphamide CP is an anticancer agent that is widely used in the treatment of pediatric and adult malignancies. CP is also known as an antirheumatic and anti-inflammatory drug Brummaier et al. CP is a prodrug that requires enzymatic bioactivation to produce its therapeutic function Raccor et al. There is a significant variation in the plasma levels of CP ranging from 1. According to in vitro studies, it is clear that genetic polymorphisms in CYP2B6 gene and interindividual differences in the CYP2B6 enzymatic activity are associated with variability in CP efficacy Roy et al. Very limited clinical studies have evaluated the impact of CYP2B6 variants on patient exposure to CP, instead, many studies have investigated the influence of patient genotype on therapeutic outcome or treatment efficacy of CP. However, Shu et al. Patients with the GG genotype had the worse outcome compared to patients with the wild type allele. Variability in CYP2B6 polymorphisms between populations indicates that cancer patients in various ethnicities will respond variably to CP therapy. According to research, the number of cancer survivals vary between and within countries. These differences are partly due to limited access to high quality and effective treatment in some part of the world Newton et al. However, the majority of cancer patients living in LMICs have limited access to essential medicine and sometimes imported medication are either counterfeits or of poor quality Fernandez et al. Cancer care is not included in most resource limited settings due to high cost, as such, patients have to pay for cancer treatment out of their pocket Eniu et al. Important barriers to availability and affordability of anticancer drugs include lack of governmental reimbursement, allocation of healthcare budgets, generic and biosimilar products as well as the right to patent Renner et al. Therefore, patients in these regions are likely to experience drug resistance, treatment failure and more ADRs than those in HICs Newton et al. Additionally, increase number of adverse outcome is expected to occur in Africa, Asia and some parts of Europe, where other diseases such as HIV, tuberculosis and hepatitis are found amongst cancer patients who are self-sponsored without any health care coverage and reduced compliance to medication due to lack of funds and timely treatment ACTION Study Group, ; Eniu et al. Therefore, in addition to other confounders, increased accessibility to essential medicine, availability of health care coverage, special care for patients with comorbidity and genotyping of patients may improve therapy. Bupropion, generally used as an antidepressant, was later recommended as a non-nicotine treatment for smoking cessation. It is approved for treatment of nicotine dependence in patients with tobacco use disorder Jorenby et al. It acts by increasing dopaminergic and noradrenergic transmission via the blockage of neurotransmitter reuptake at the synapse thereby antagonizing the effects of nicotine acetylcholine receptor leading to nicotine withdrawal Paterson et al. Also, bupropion is prescribed alone or in combination with other antidepressants for treatment of major depressive disorder and seasonal affective disorder. It is used as an adjunctive medication to reverse antidepressant-associated sexual dysfunction and to improve the efficacy of other antidepressants in partial or non-responders Fava et al. Both bupropion and the active metabolite S-hydroxybupropion are responsible for the antidepressant and smoking cessation effect of bupropion Zhu et al. Depending on the patient's genotype, they can experience either increased or decreased exposure to the active metabolite hydroyxbupropion compared to wild type Kirchheiner et al. Reportedly, patients harboring at least one reduced function allele had reduced exposure to the active metabolite and a lower clearance of the parent drug Kirchheiner et al. Meanwhile, those with at least one increased function allele have increased exposure to hydroxyl active metabolites and a higher clearance of the parent drug Kirchheiner et al. Some studies have linked patient genotype to the efficacy of bupropion as a smoking cessation agent. Specifically, patients with the AA genotype wild type succeeded in ceasing smoking compared to those with the variant genotype AG and GG Tomaz et al. The increase function alleles might have led to higher clearance of the drug as well as reduced efficacy. There are some differences in experimental outcome, for example, in a clinical trial involving African American light smokers, a direct association between CYP2B6 genotype and smoking cessation was not observed, according to the authors, poor adherence amongst the participants might have led to the observed results. Most studies did not assess the impact of CYP2B6 polymorphisms on the antidepressant effect of bupropion. Compared to HICs, mental health in LMICs is still limited with low number of clinical trials and extremely low number of patients receiving treatment Sankoh et al. Individuals with serious mental health problems in Nigeria cannot have access to health care due to the limited number of resources and mental health staff Chibanda et al. Approximately, psychiatric doctors serve a population of about million people. Currently, these issues are being addressed by the Nigerian government via the forthcoming Mental Health and substance abuse bill Brathwaite et al. Another study involving prescriptions and case records of patients who were placed on antidepressants showed that tricyclic antidepressants were the most prescribed drugs Amitriptyline hydrochloride, fluoxetine, clomipramine, escitalopram, and imipramine hydrochloride are the antidepressants found on the WHO list of essential medicine for Nigeria WHO, 3. In Zimbabwe, a research made in indicated that psychiatrists sometimes experience shortage of drugs which results in relapse among patients Kidia et al. The antidepressants available were old generation drugs with many side effects Kidia et al. According to one of the psychiatrists, more attention is being given to people with HIV than those with mental health, furthermore mental health policies were never implemented because of inadequate funding Kidia et al. The African Mental Health Research Initiative group aims to create awareness and strengthen the mental health sector via research and capacity building in Sub-Saharan Africa Chibanda et al. In some countries bupropion is available in the pharmacy with prescription. In others, it is found in general stores without prescription Langhaug et al. Meanwhile, for some countries, data for the use of bupropion is not available. For example, GHO data shows that in Germany, France, Australia, Canada, United States of America, Congo, and India bupropion is available in pharmacies with prescription, whereas in Nigeria, it is found in general stores without prescription, in Malaysia, Ukraine, Zimbabwe, and Cameroon, GHO data shows that bupropion was present in pharmacy with prescription. Though bupropion is cost effective and widely used in most countries, its application as a smoking cessation agent is still very limited in some LMICs. MPOWER measure is a tobacco free initiative established by WHO for defeating the global tobacco epidemic via M onitoring tobacco use, P rotecting people from tobacco use, O ffering help to quit, W arning about dangers of tobacco, E nforcing bans on advertising and sponsorship and R aising taxes on tobacco in all parts of the world Batini et al. According to a recent report by Batini et al. Using the African continent as an example, authors report that pharmacotherapy for smoking cessation is scarce in Nigeria with few pharmacies offering nicotine replacement therapy. In Tanzania, nicotine replacement therapy is available and smoking cessation therapy has been introduced into the methadone clinic in Dar es Salaam Batini et al. However, the use of non-nicotine therapy such as bupropion is still lacking in these countries. Depression seems to coexist with many diseases that are common in both high and LMICs. In India, high prevalence of depressive episodes were found among diabetic patients Kanwar et al. In a comparison between Ethiopian and German cancer patients, depression and anxiety were found in both groups, but a little higher among uneducated Ethiopian patients Wondie et al. Considering the fact that some HIV and cancer patients in LMICs are not able to afford treatment, depression might be high among these group of patients. It is well-established that CYP2B6 genotype is a significant contributor to variability in hydroxybupropion and bupropion levels, influencing the efficacy of bupropion therapy in smoking cessation patients. Knowledge on CYP2B6 genotype in consideration with other factors might give a clue on patients who are likely to benefit from therapy. Constant supply of bupropion could help to reduce relapse among patients in most LMICs. Treatments of other comorbidities that are risk factors of depression have the potential to improve therapy and reduce the number of depressive patients worldwide. There is need to create awareness in the area of mental health via research and innovation, including capacity building, training more mental health staff and psychiatric doctors in LMICs. Ketamine is a World Health Organization Essential Medicine widely used for perioperative, acute and chronic pain, and sedation. It is used either solely or in combination with opioids for the management of acute post-operative and chronic refractory pain Laskowski et al. Its use in the management of status epilepticus, bipolar disorder, suicidal behavior, major depressive disorder and treatment resistant depression has been demonstrated Yeh et al. Ketamine acts as a non-competitive antagonist of the N-Methyl-D-aspartic acid receptor blocking its action, thereby preventing the development and chronification of pain Noppers et al. Variability in the expression and catalytic activity of CYP2B6 variant enzymes results in differences in the hepatic clearance of ketamine Wang et al. Individual differences in hepatic blood flow leading to differences in patient clearance of the drug has also been implicated Yanagihara et al. Although there were no direct associations between the genotype of the patients and the occurrence of ADRs, drowsiness and hallucination were more often observed in patients with lower clearance than those with higher clearance. The authors hypostatized that higher plasma concentrations due to reduced clearance may have predisposed patients to ketamine ADRs. In vitro studies further demonstrate that CYP2B6 variants confer variability in the metabolism of ketamine. This indicates that patients harboring different CYP2B6 variants will respond differently to the drug Borsato et al. Therefore, knowing the genotype of the patient prior to prescription could help to address individual needs and reduce ADRs. There is a huge difference in availability and application of anesthesia between high and LMICs as reviewed by Dolman et al. Factors influencing these differences include limited physician anesthesiologists and nurse anesthetists, insufficient anesthesia equipment and infrastructure, patient comorbidities and late presentations LeBrun et al. In LMICs, ketamine is the only anesthetic drug in many hospitals as compared to HICs, where it is used as an adjunct in combination with other anesthetics Dohlman, LMICs are lacking in the provision and training for safe anesthesia practice. In Nigeria, intravenous ketamine is used as general anesthesia in parts of the country where anesthesiologist's services are scarce. However, few patients experience adverse effects including high blood pressure, priapism, emergent delirium, tachycardia, disorientation and confusion Iyalomhe and Iyalomhe, In a recent survey conducted in Tanzania, Malawi and Zambia, ketamine was widely used in many of the hospitals to compensate for shortages of other forms of anesthesia. Anesthesia care in these countries were performed by non-physician anesthetists, some of whom had no formal training. Shortage of staff, interrupted access to electricity and water for some facilities and lack of functional anesthesia machines were reported Gajewski et al. Though ketamine is considered safe, its application by untrained personal might lead to abnormal doses and contribute to adverse effects in these populations. Methadone is a synthetic opioid utilized for the treatment of chronic, acute and neuropathic pain. It is also used as an analgesic to treat pain in cancer patients and as a maintenance therapy for opiate addiction Chou et al. In opioid use disorder, methadone reduces the painful symptoms of opiate withdrawal and relieves drug craving by acting on the opioid receptor in the brain. Methadone is administered as a racemate consisting of the S -and R -enantiomers Crettol et al. Studies also show that CYP2B6 genotype influences the severity of neonatal abstinence syndrome Mactier et al. The presence of concomitant diseases such as HCV infection influence methadone therapy. Reportedly, HCV patients often require higher doses of methadone. Thus, patients are likely to experience unwanted effects of the drug. Therefore, dose reduction in this group of patients may yield methadone safety. Even though methadone maintenance therapy is effective and affordable, it is still unavailable in many LMICs where it is highly needed. As reported in , out of countries with evidence of drug use disorder, opioid substitution therapy OST was available in only 86 countries Avert, ; International HR, OST is a replacement therapy whereby prescribed medications such as methadone and buprenorphine are given to opioid dependent patients, which enables them to reduce or cease from injecting drugs. However, the Nigerian government has initiated guidelines on the use of methadone for treatment of drug rehabilitation International HR, However, in Germany opiate substitution treatment is variable between people in prison and those living outside of prison. There is need for the government to provide funds for the health care in some LMICs. Artemisinin-based combination therapy ACT is the basis of treatment and considered first-line for the majority of malaria infection cases WHO, ACT, presently approved for treatment of uncomplicated Plasmodium falciparum malaria in many malaria-endemic countries, are substrates of CYP enzymes Svensson and Ashton, Combining artemisinin agents, which are fast acting with a short half-life with partner drugs that have long half-life enables optimization of parasite killing and greatly protects against reinfection White et al. Patient's response to antimalarial treatment can be influenced by factors such as quality of the antimalarial agent, the natural immune system of the host, parasite resistance, concomitant diseases and the pharmacokinetics of the malaria drug Travassos and Laufer, Most studies on the efficacy of antimalarial agents have focused more on understanding the resistant mechanism of the parasite by investigating the parasites multi drug resistant genes Travassos and Laufer, However, studies have shown interindividual variations in the concentration of artimisinin, dihydroartemisinin, artesunate, and their anti-malarial effect among malaria infected individuals. Underdosing seems to enhance parasite resistance to the therapeutic agents. Due to the lack of efficacy, optimization of antimalarial treatment is the main factor considered toward global eradication of the diseases WHO, Among many other factors, host genetics, especially polymorphisms in CYP enzymes involved in the metabolism of the drugs, may be one of the confounders, causing variability in ACT drugs levels and treatment failure. Authors did not evaluate the direct impact of these polymorphisms on treatment outcome or safety of the drugs Marwa et al. The authors showed that decreased exposure to artemether and desbutyl-lumefantrine caused by NVR was further enhanced by patients with CYP2B6 GG genotype ultrarapid metabolizers Abdullahi et al. Limited effort has been employed to determine genetic polymorphisms in CYP enzymes, which may lead to therapeutic failure in patients who are extensive metabolizers or cause toxicity and resistance in patients who are slow metabolizers Gil, ACT is an effective treatment for resistant malaria, knowledge on polymorphisms influencing their efficacy may help to improve malaria therapy. The fight against over the counter drugs will help to reduce relapse among patients and improve the lives of people in the rural population. Over the counter poor quality malaria drugs, some of which have no active ingredients, are offered especially by smaller vendors Bassat et al. In Uganda, compared to the urban population, the rural populations spent more money and experienced This article provides evidence on CYP2B6 functional variability in drug metabolism and exposure across populations. The impact of CPY2B6 variant on patient response to various substrates is evident in most ethnicities involved in this study. Depending on CYP2B6 genotype, patients may be vulnerable to ADRs ranging from mild to severe due to increased exposure to active oral drugs, or otherwise experience therapeutic failure due to reduced exposure to active metabolite in the case of prodrugs. Poor metabolizers are likely to experience more ADRs active compounds or treatment failure prodrugs than intermediate or normal metabolizers. Due to the increasing knowledge on the role of CYP2B6 enzyme in drug metabolism, there is the need to evaluate other CYP2B6 variants on substrate metabolism in various populations or ethnicity. Researchers can make use of the publicly available pharmacogene variation PharmVar website, which clearly defines each haplotype or alleles Desta et al. CYP2B6 loss of function alleles poor metabolizer genotypes , which lead to an increase in individual active drug exposure and toxicity are frequent in some populations leading to high risk of ADRs in these populations. This may help to reduce ADRs and increase patient compliance with subsequent reduction in drug resistance due to lack of patient compliance. At the moment, many pharmacogenomics related ADRs are noticed only after the drugs have been administered to the patients. Population specific pharmacogenomics approaches at the level of drug development can be used to address differences in susceptibility to ADRs between populations. The inclusion of pharmacogenomics in clinical trials could give a clue on populations that are likely to benefit or suffer from adverse effects. This could guide dose adjustments for some populations. Previous clinical trials included individuals from African descent to represent the African population, while it is clear that the African continent demonstrates high genetic diversity. Therefore, the inclusion of a diverse population in clinical trials is inevitable. Interestingly, intrapopulation as well as inter-individual variability in CYP2B6 alleles further complicates the efficacy of many of its substrates. This could potentially be improved by the application of patient genotyping prior to prescription in clinical practice. Thus, a robust and more personalized therapy could be provided to the patients. Thus, pharmacovigilance is urgently needed in these populations for the detection and subsequent prevention of ADRs. Higher donor dependency and cost of medication has been highlighted as barriers to the accessibility of quality and less toxic drugs in LMICs. Donor funding has saved many lives in LMICs for the past decades. The help from richer countries is provided in the form of finance or medication via Government officials or private agencies in health sectors. With the growing population in LMICs, it is evident that donor funding can no longer benefit every individual. Therefore, in this era, donors should focus more on human capacity building and establishment of infrastructures that will help LMICs become independent or self-sponsored Pillai et al. For example, antiretroviral drugs are manufactured and sold at a cheaper rate in India compared to African countries, where drugs are mostly imported at a very high cost Dickson, The African pharmaceutical industry, for example, could be expanded and strengthened. This could help to remove financial barriers to medicines as well as to improve access to more potent, expensive, less toxic medication. The public health sector needs to fully support organizations such as the African Pharmacogenomics Consortium APC , which seeks to address the issue of drug safety, financial problems in the health care sector, disease burden, research training and implementation of pharmacogenomics in Africa Dandara et al. There is a need for creating awareness, funding and provision of medication in countries where mental health has been neglected. For example, a significant reduction of heroin use and improvement of mental health was observed among participants who were retained for methadone therapy for 6 months in South Africa Scheibe et al. There is a need for amendments of foreign and government policies, that limit the growth of health care. According to Tomlinson et al. The government in LMICs needs to develop strategies to raise internal funds to support health care rather than solely depending on foreign aid. There is a need for allocation of healthcare budgets in both public and private sectors. Additionally, accountability and better amendment of funds in healthcare can help to improve health care services. People with two or more diseases need special attention and health care coverage, for example, people with HCV and HIV coinfection. Thus, increasing health coverage and accessibility to diagnosis and counseling by trained medical staffs can help patients to receive the right therapy and avoid drug-drug interactions due to concomitant use of HIV and HCV drugs. In conclusion, there is a high level of CYP2B6 genetic variability between and within ethnicities. In addition to other confounders that can affect the pharmacokinetics and pharmacodynamics properties of a drug, CYP2B6 genotyping could be considered in regards to all CYP2B6 substrates prescriptions in populations with expected high variability and drugs with narrow therapeutic window. JS developed the presented idea, supervised the manuscript progress and data analysis, and published own data on CYP2B6 pharmacogenetics. IL did the systematic review of the literature, evaluated, analyzed the impact of the CYP2B6 alleles on drug safety in a global view, and wrote the manuscript. All authors contributed to the article and approved the submitted version. This project has received funding from the European Union's Horizon research and innovation program under Grant Agreement No. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Tobacco Free Initiative. Abdullahi, S. Agents Chemother. Policy and priorities for national cancer control planning in low- and middle-income countries: lessons from the Association of Southeast Asian Nations ASEAN Costs in Oncology prospective cohort study. Agbaji, O. Agency, E. Google Scholar. Ahmad, T. Aitken, A. Drug Metab. Alhassan, Y. BMC Public Health Aminkeng, F. Higher frequency of genetic variants conferring increased risk for ADRs for commonly used drugs treating cancer, AIDS and tuberculosis in persons of African descent. Pharmacogenomics J. Ampadu, H. Drug Saf. Ansermot, N. Ariyoshi, N. QH replacement overcomes effects on the metabolism of cyclophosphamide and efavirenz caused by CYP2B6 variant with Arg Avert Bachanova, V. Blood Marrow Transplant 21, — Bank, P. Estimated nationwide impact of implementing a preemptive pharmacogenetic panel approach to guide drug prescribing in primary care in The Netherlands. BMC Med. Bart, G. Ethnic and genetic factors in methadone pharmacokinetics: a population pharmacokinetic study. Drug Alcohol Depend. Bassat, Q. Combating poor-quality anti-malarial medicines: a call to action. Batey, M. Population pharmacokinetics of adjuvant cyclophosphamide, methotrexate and 5-fluorouracil CMF. Cancer 38, — Batini, C. Smoking cessation on the African continent: challenges and opportunities. Care Med. Bazargani, Y. Essential medicines for breast cancer in low and middle income countries. BMC Cancer Benowitz, N. Influence of CYP2B6 genetic variants on plasma and urine concentrations of bupropion and metabolites at steady state. Bielinski, S. Preemptive genotyping for personalized medicine: design of the right drug, right dose, right time-using genomic data to individualize treatment protocol. Mayo Clin. Birbal, S. Adverse drug reactions associated with antiretroviral therapy in South Africa. AIDS Res. Borsato, G. Ketamine in seizure management and future pharmacogenomic considerations. Bourgi, K. Greater weight gain in treatment-naive persons starting dolutegravir-based antiretroviral therapy. Brathwaite, R. Predicting the risk of future depression among school-attending adolescents in Nigeria using a model developed in Brazil. Psychiatry Res. Bray, J. Influence of pharmacogenetics on response and toxicity in breast cancer patients treated with doxorubicin and cyclophosphamide. Cancer , — Brummaier, T. Using cyclophosphamide in inflammatory rheumatic diseases. Calcagno, A. Carr, D. CYP2B6 c. Chaivichacharn, P. Dosage optimization of efavirenz based on a population pharmacokinetic-pharmacogenetic model of HIV-infected patients in Thailand. Chibanda, D. Mental health research capacity building in sub-Saharan Africa: the African mental health research initiative. Health Camb 7:e8. Chou, R. Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. Pain 10, — Ciccacci, C. Nevirapine-induced hepatotoxicity and pharmacogenetics: a retrospective study in a population from Mozambique. Pharmacogenomics 11, 23— Clark, S. Cohen, K. PubMed Abstract Google Scholar. Coles, R. Crettol, S. Csajka, C. Population genetic-based pharmacokinetic modeling of methadone and its relationship with the QTc interval in opioid-dependent patients. Pharmacokinet 55, — Dandara, C. African pharmacogenomics consortium: consolidating pharmacogenomics knowledge, capacity development and translation in Africa: Consolidating pharmacogenomics knowledge, capacity development and translation in Africa. AAS Open Res. David, S. Pharmacogenetic clinical trial of sustained-release bupropion for smoking cessation. Nicotine Tob Res. Clinical pharmacokinetics of cyclophosphamide. Pharmacokinet 44, — Desta, Z. Stereoselective and regiospecific hydroxylation of ketamine and norketamine. Xenobiotica 42, — Dhoro, M. BMC Pharm. Toxicol Dickson, D. Indian company offers cheap anti-AIDS drugs. Nature Dohlman, L. Providing anesthesia in resource-limited settings. Dolgin, E. Preemptive genotyping trialed to prevent adverse drug reactions. Drozda, K. Pharmacogenetic labeling of FDA-approved drugs: a regulatory retrospective. Eap, C. Ekins, S. Molecular characterization of CYP2B6 substrates. Further characterization of the expression in liver and catalytic activity of CYP2B6. Eniu, A. Cancer medicines in Asia and Asia-Pacific: what is available, and is it effective enough? ESMO Open 4:e Evans, W. Moving towards individualized medicine with pharmacogenomics. Nature , — Falk, M. Association of CYP2B6 genotype with survival and progression free survival in cyclophosphamide treated multiple myeloma. Cancer Ther. Faucette, S. Regulation of CYP2B6 in primary human hepatocytes by prototypical inducers. Fava, M. Prim Care Companion J. Psychiatry 7, — Fernandez, F. Poor quality drugs: grand challenges in high throughput detection, countrywide sampling, and forensics in developing countries. Analyst , — Gadel, S. Differences in methadone metabolism by CYP2B6 variants. Gajewski, J. Anesthesia capacity of district-level hospitals in malawi, tanzania, and zambia: a mixed-methods study. Giacomelli, A. Clinical and genetic determinants of nevirapine plasma trough concentration. Giardina, C. Gil, J. Malaria pharmacogenomics: return to the future. Pharmacogenomics 14, — Gokengin, D. Gounden, V. Griskevicius, L. Bioactivation of cyclophosphamide: the role of polymorphic CYP2C enzymes. Hananta, L. Osong Public Health Res. Hanna, I. Expression of human cytochrome P 2B6 in Escherichia coli : characterization of catalytic activity and expression levels in human liver. Hardy, J. Randomized, double-blind, placebo-controlled study to assess the efficacy and toxicity of subcutaneous ketamine in the management of cancer pain. Helsby, N. Hesse, L. Pharmacogenetic determinants of interindividual variability in bupropion hydroxylation by cytochrome P 2B6 in human liver microsomes. Pharmacogenetics 14, — Hidestrand, M. CYP2B6 and CYP2C19 as the major enzymes responsible for the metabolism of selegiline, a drug used in the treatment of Parkinson's disease, as revealed from experiments with recombinant enzymes. Hijazi, Y. Hofmann, M. Aberrant splicing caused by single nucleotide polymorphism c. Hung, C. Pharmacogenomics 12, — International HR Global State of Harm Reduction. Global State of Harm Reduction: Updates. Iyalomhe, G. Intravenous ketamine anaesthesia: a year experience in a sub-urban hospital in nigeria. Johnson, G. Blood , — Jorenby, D. A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation. Kanwar, N. Prevalence of psychiatric comorbidity among patients of type 2 diabetes mellitus in a hilly state of North India. Kharasch, E. Intraoperative methadone: rediscovery, reappraisal, and reinvigoration? Common polymorphisms of CYP2B6 influence stereoselective bupropion disposition. Methadone disposition: implementing lessons learned. Methadone pharmacogenetics: CYP2B6 polymorphisms determine plasma concentrations, clearance, and metabolism. Anesthesiology , — Kidia, K. Mental health in Zimbabwe: a health systems analysis. Lancet Psychiatry 4, — Kim, G. Role of preemptive genotyping in preventing serious adverse drug events in South Korean patients. Drug Saf 40, 65— Kirchheiner, J. Pharmacogenetics 13, — Kouanfack, C. Dolutegravir-based or low-dose efavirenz-based regimen for the treatment of HIV Kringen, M. Combined effect of CYP2B6 genotype and other candidate genes on a steady-state serum concentration of methadone in opioid maintenance treatment. Drug Monit. The analgesic effect of intravenous ketamine and lidocaine on pain after spinal cord injury. Acta Anaesthesiol. Labarga, P. Hepatotoxicity of antiretroviral drugs is reduced after successful treatment of chronic hepatitis C in HIV-infected patients. Laib, A. Serum concentrations of hydroxybupropion for dose optimization of depressed patients treated with bupropion. Lang, T. Extensive genetic polymorphism in the human CYP2B6 gene with impact on expression and function in human liver. Pharmacogenetics 11, — Langhaug, L. Health Syst. Larney, S. Global, regional, and country-level coverage of interventions to prevent and manage HIV and hepatitis C among people who inject drugs: a systematic review. Lancet Glob. Health 5:e—e Laskowski, K. A systematic review of intravenous ketamine for postoperative analgesia. LeBrun, D. Prioritizing essential surgery and safe anesthesia for the Post Development Agenda: operative capacities of 78 district hospitals in 7 low- and middle-income countries. Surgery , — Lee, A. CYP2B6 genotype alters abstinence rates in a bupropion smoking cessation trial. Psychiatry 62, — Lee, W. Lewis, D. Molecular modelling of mammalian CYP2B isoforms and their interaction with substrates, inhibitors and redox partners. Xenobiotica 27, — Li, J. Pharmacogenomics 13, — Li, Y. Liptrott, N. The impact of cytokines on the expression of drug transporters, cytochrome P enzymes and chemokine receptors in human PBMC. Lo, R. Estrogen receptor-dependent regulation of CYP2B6 in human breast cancer cells. Acta , — Anesthesia for cesarean delivery: a cross-sectional survey of provincial, district, and mission hospitals in Zimbabwe. Lonsdale, J. The genotype-tissue expression GTEx project. Lynch, T. The effect of cytochrome P metabolism on drug response, interactions, and adverse effects. Macarayan, E. The quality of malaria care in 25 low-income and middle-income countries. BMJ Glob Health 5:e Mactier, H. Variations in infant CYP2B6 genotype associated with the need for pharmacological treatment for neonatal abstinence syndrome in infants of methadone-maintained opioid-dependent mothers. Manosuthi, W. Marwa, K. Cytochrome P single nucleotide polymorphisms in an indigenous Tanzanian population: a concern about the metabolism of artemisinin-based combinations. Masimirembwa, C. Rolling out efavirenz for HIV precision medicine in Africa: are we ready for pharmacovigilance and tackling neuropsychiatric adverse effects? Omics 20, — Mayston, R. Explanatory models of depression in sub-Saharan Africa: synthesis of qualitative evidence. Mehlotra, R. Mhandire, D. Omics 19, — Medicc Rev Mukonzo, J. CYP2B6 genotype-based efavirenz dose recommendations during rifampicin-based antituberculosis cotreatment for a sub-Saharan Africa population. Pharmacogenomics 17, — Influence of efavirenz pharmacokinetics and pharmacogenetics on neuropsychological disorders in Ugandan HIV-positive patients with or without tuberculosis: a prospective cohort study. BMC Infect. Dis Nampala, H. Ndashimye, E. Poverty Nebert, D. Human cytochromes P in health and disease. R Soc. B Biol. Newton, P. Impact of poor-quality medicines in the 'developing' world. Trends Pharmacol. Noppers, I. Ketamine for the treatment of chronic non-cancer pain. Oyinlade, A. Palacharla, R. Quantitative in vitro phenotyping and prediction of drug interaction potential of CYP2B6 substrates as victims. Xenobiotica 48, — Parsons, H. Methadone initiation and rotation in the outpatient setting for patients with cancer pain. Patel, T. Mortality among patients due to adverse drug reactions that lead to hospitalization: a meta-analysis. Paterson, N. Chronic bupropion attenuated the anhedonic component of nicotine withdrawal in rats via inhibition of dopamine reuptake in the nucleus accumbens shell. Paula, D. Impact of protocol change on individual factors related to course of adverse reactions to chemotherapy for breast cancer. Care Cancer 28, — Pearce, R. Developmental expression of CYP2B6: a comprehensive analysis of mRNA expression, protein content and bupropion hydroxylase activity and the impact of genetic variation. Perez-Ruixo, C. Population pharmacokinetics of esketamine nasal spray and its metabolite noresketamine in healthy subjects and patients with treatment-resistant depression. Pharmgkb Pillai, G. The Next Generation Scientist program: capacity-building for future scientific leaders in low- and middle-income countries. Pizzi, M. Transition from intravenous to enteral ketamine for treatment of nonconvulsive status epilepticus. Intensive Care Portmann, S. Enantioselective capillary electrophoresis for identification and characterization of human cytochrome P enzymes which metabolize ketamine and norketamine in vitro. A , — Raccor, B. Potential contribution of cytochrome P 2B6 to hepatic 4-hydroxycyclophosphamide formation in vitro and in vivo. Rajman, I. African genetic diversity: implications for cytochrome pmediated drug metabolism and drug development. EBioMedicine 17, 67— Rakhmanina, N. Efavirenz in the therapy of HIV infection. Expert Opin. Rendic, S. Summary of information on human CYP enzymes: human P metabolism data. Renner, L. The role of generic medicines and biosimilars in oncology in low-income countries. Rocha, V. Association of drug metabolism gene polymorphisms with toxicities, graft-versus-host disease and survival after HLA-identical sibling hematopoietic stem cell transplantation for patients with leukemia. Leukemia 23, — Roy, P. Development of a substrate-activity based approach to identify the major human liver P catalysts of cyclophosphamide and ifosfamide activation based on cDNA-expressed activities and liver microsomal P profiles. Ruff, P. Access to cancer therapeutics in low- and middle-income countries. Book , 58— Sankoh, O. Mental health in Africa. Lancet Global Health 6, e—e5. Sarfo, F. Pharmacogenetic associations with plasma efavirenz concentrations and clinical correlates in a retrospective cohort of Ghanaian HIV-infected patients. Sax, P. Weight gain following initiation of antiretroviral therapy: risk factors in randomized comparative clinical trials. Scheibe, A. Six-month retention and changes in quality of life and substance use from a low-threshold methadone maintenance therapy programme in Durban, South Africa. Practice Schipani, A. Integration of population pharmacokinetics and pharmacogenetics: an aid to optimal nevirapine dose selection in HIV-infected individuals. Schnoll, R. Current and emerging pharmacotherapies for treating tobacco dependence. Drugs 11, — Schurig, A. Sevko, A. Cyclophosphamide promotes chronic inflammation-dependent immunosuppression and prevents antitumor response in melanoma. Shu, W. Cytochrome P genetic variations can predict mRNA expression, cyclophosphamide 4-hydroxylation, and treatment outcomes in chinese patients with non-hodgkin's lymphoma. Siedner, M. Reduced efficacy of HIV-1 integrase inhibitors in patients with drug resistance mutations in reverse transcriptase. Srivastava, A. Quantifying the metabolic activation of nevirapine in patients by integrated applications of NMR and mass spectrometries. Stingl, J. Genetic variability of drug-metabolizing enzymes: the dual impact on psychiatric therapy and regulation of brain function. Psychiatry 18, — Opioid substitution therapy for people living in German prisons—inequality compared with civic sector. Su, S. Svensson, U. Identification of the human cytochrome P enzymes involved in the in vitro metabolism of artemisinin. Synowiec, A. Ketamine use in the treatment of refractory status epilepticus. Epilepsy Res. Talal, A. Toward precision prescribing for methadone: Determinants of methadone deposition. Thorn, C. Genomics 20, — Tomaz, P. CYP2B6 rs polymorphism is associated with smoking cessation success in bupropion therapy. Tomlinson, C. How patent law reform can improve affordability and accessibility of medicines in South Africa: Four medicine case studies. South Afr. Travassos, M. Resistance to antimalarial drugs: molecular, pharmacologic, and clinical considerations. Pediatric Res. Ugochukwu, O. The time is now: reforming Nigeria's outdated mental health laws. Lancet Global Health 8, e—e Uttayamakul, S. Vardhanabhuti, S. Clinical and genetic determinants of plasma nevirapine exposure following an intrapartum dose to prevent mother-to-child HIV transmission. Victorri-Vigneau, C. Vitoria, M. The transition to dolutegravir and other new antiretrovirals in low-income and middle-income countries: what are the issues? Aids 32, — Walker, E. Are we doing enough to prevent poor-quality antimalarial medicines in the developing world? Wang, H. Glucocorticoid receptor enhancement of pregnane X receptor-mediated CYP2B6 regulation in primary human hepatocytes. Wang, P. Stereoselective bupropion hydroxylation by cytochrome P CYP2B6 and cytochrome P oxidoreductase genetic variants. Weinshilboum, R. Inheritance and drug response. White, N. Lancet , — WHO Guidelines for the Treatment of Malaria - Third edition. Wondie, Y. Wu, P. Wu, Z. Scaling up opioid dependence treatment in low- and middle-income settings. World Health Organ —A. Xie, H. Role of polymorphic human CYP2B6 in cyclophosphamide bioactivation. Yanagihara, Y. Involvement of CYP2B6 in n-demethylation of ketamine in human liver microsomes. Yang, H. PLoS Genet e Yeh, P. Oral ketamine controlled refractory nonconvulsive status epilepticus in an elderly patient. Seizure 20, — Yimer, G. Yoon, H. Effects of CYP2B6 polymorphisms on plasma nevirapine concentrations: a systematic review and meta-analysis. Zahari, Z. Drug Alcohol Depend , — Zakeri, S. Iran Med. Zanger, U. Cytochrome P enzymes in drug metabolism: Regulation of gene expression, enzyme activities, and impact of genetic variation. Zash, R. Neural-tube defects and antiretroviral treatment regimens in botswana. Zhang, Y. Pharmacokinetic and pharmacodynamic responses to clopidogrel: evidences and perspectives. Public Health Zhu, A. CYP2B6 and bupropion's smoking-cessation pharmacology: the role of hydroxybupropion. Keywords: drug metabolism, adverse drug reaction, cytochrome P 2B6, genetic polymorphism, drug safety, pharmacogenetics, pharmacogenomics, personalized medicine. The use, distribution or reproduction in other forums is permitted, provided the original author s and the copyright owner s are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Stingl, jstingl ukaachen. Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher. Top bar navigation. About us About us. Sections Sections. About journal About journal. Article types Author guidelines Editor guidelines Publishing fees Submission checklist Contact editorial office. Pharmacogenetics and Pharmacogenomics. Immaculate M. Langmia 1 Katja S. Introduction Adverse drug reactions ADRs are globally one of the major causes of morbidity and mortality Giardina et al. Table 1. Drug substrates known for metabolism by the CYP2B6 enzyme.

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