Association between CYP3A4, CYP3A5 and ABCB1 genotype and tacrolimus treatment outcomes among allogeneic HSCT patients.

Aim: Successful treatment with tacrolimus to prevent graft versus host disease (GVHD) and minimize tacrolimus-related toxicities among allogeneic hematopoietic cell transplantation (alloHCT) recipients is contingent upon quickly achieving and maintaining concentrations within a narrow therapeutic range. The primary objective was to investigate associations between CYP3A4, CYP3A5 or ABCB1 genotype and the proportion of patients that attained an initial tacrolimus goal concentration following initiation of intravenous (iv.) and conversion to oral administration. Materials & methods: We retrospectively evaluated 86 patients who underwent HLA-matched (8/8) related donor alloHCT and were prescribed a tacrolimus-based regimen for GVHD prophylaxis. Results & conclusion: The findings of the present study suggests that CYP3A5 genotype may impact attainment of initial therapeutic tacrolimus concentrations with oral administration in alloHCT recipients.

Role of CYP2B6 pharmacogenomics in bupropion-mediated smoking cessation.

WHAT IS KNOWN AND OBJECTIVE: Pharmacogenomics holds promise in smoking cessation because of its potential to shed light on the complexity of drug metabolism and improve treatments using therapeutic agents. The cytochrome P450 2B6 gene (CYP2B6) encodes CYP2B6 enzyme that has been found to mediate the hydroxylation of bupropion, a smoking cessation aid. CYP2B6 exhibits a range of polymorphic variants that alter the pharmacokinetics and pharmacodynamics of bupropion. Genetic variations in CYP2B6 may influence the risk of adverse effects or efficacy of treatment with bupropion. The objective of this review was to investigate the influence of pharmacogenomics on smoking cessation therapy. METHODS: A thorough literature search was conducted on PubMed, SCOPUS and EMBASE using keywords related to bupropion, smoking cessation, pharmacogenomics and CYP2B6. Research and review articles, case reports and clinical and preclinical studies pertinent to the research topic were identified, evaluated and summarized. Cited articles within the above-mentioned sources also provided pertinent information. RESULTS: There is strong literature evidence to prove that CYP2B6 polymorphisms affect pharmacokinetic and pharmacodynamic properties of bupropion, thus affecting the therapeutic outcome of smoking cessation therapy. WHAT IS NEW AND CONCLUSIONS: Complete understanding of pharmacogenetic variation of bupropion pharmacokinetics and pharmacodynamics will be beneficial for designing safer and more personalized smoking cessation therapy with improved outcomes.