Background: Drug-metabolizing enzymes play a role in chemical carcinogenesis through enzymatic activation of procarcinogens to biologically reactive metabolites. The role of gene polymorphisms of several cytochrome P450 enzymes in digestive cancer risk has been extensively investigated. However, the drug-metabolizing enzymes with the broader substrate specificity, CYP3A4 and CYP3A5, have not be...

PURPOSE The purpose is to identify the demographic, physiologic, and inheritable factors that influence CYP3A activity in cancer patients. EXPERIMENTAL DESIGN A total of 134 patients (62 females; age range, 26 to 83 years) underwent the erythromycin breath test as a phenotyping probe of CYP3A. Genomic DNA was screened for six variants of suspected functional relevance in CYP3A4 (CYP3A4*1B, CY...

AIMS Clopidogrel is an antiplatelet drug primarily used to treat or prevent acute ischemic stroke (IS) or myocardial infarction (MI). This prodrug requires biotransformation to an active metabolite by cytochrome P450 (CYP) enzymes, and CYP single nucleotide polymorphisms (SNPs) could affect the efficiency of such biotransformation. METHODS A total of 375 consecutive IS patients were genotyped...

Cyclosporine, everolimus, and tacrolimus are the cornerstone of immunosuppressive therapy in renal transplantation. These drugs are characterized by narrow therapeutic windows, highly variable pharmacokinetics (PK), and metabolism by CYP3A enzymes. Recently, the decreased activity allele, CYP3A4*22, was described as a potential predictive marker for CYP3A4 activity. This study investigated the ...

Members of the cytochrome P450 3A subfamily catalyze the metabolism of endogenous substrates, environmental carcinogens, and clinically important exogenous compounds, such as prescription drugs and therapeutic agents. In particular, the CYP3A4 and CYP3A5 genes play an especially important role in pharmacogenetics, since they metabolize >50% of the drugs on the market. However, known genetic var...

A recent publication by Lu et al. (2014) described the effects of the CYP3A5 genotype on Selzentry/Celsentri (maraviroc) concentrations. Maraviroc is a chemokine (C-C motif) receptor 5 inhibitor approved for the treatment of human immunodeficiency virus (HIV) infection (Dorr et al., 2005). Maraviroc pharmacokinetics in subjects who were heterozygous (n = 8; one CYP3A5*1 and one dysfunctional al...

PurposePatients after Heart Transplant (HT) requires immune suppression with corticosteroids, mycophenolate and tacrolimus. Tacrolimus is an integral part of immunosuppression HT metabolized by the CYP3A5 pathway. There are fast, intermediate slow metabolizers Also, safety tacrolimus in these unknown. We explored utility pharmacogenomics analysis tacrolimus.MethodsThis a retrospective study 20 ...

Introduction: Pregnancy increases the clearance of CYP3A4 substrate drugs and pregnancy-related hormones (PRHs) induce hepatic expression metabolism. However, it remains unclear to what extent magnitude PRH-evoked changes in CYP3A metabolism varies across multiple substrates. This study quantified impact PRHs on protein concentrations buprenorphine human hepatocytes, compared these effects nife...

Introduction Tamoxifen therapy reduces the risk of recurrence and prolongs the survival of oestrogen-receptor-positive patients with breast cancer. Even if most patients benefit from tamoxifen, many breast tumours either fail to respond or become resistant. Because tamoxifen is extensively metabolised by polymorphic enzymes, one proposed mechanism underlying the resistance is altered metabolism...