The total CYP3A5 mRNA level is significantly greater in carriers of the CYP3A5*1 allele than in CYP3A5*3 homozygotes. Most of the CYP3A5*3 mRNA includes an intronic sequence (exon 3B) containing premature termination codons (PTCs) between exons 3 and 4. Two models were used to investigate the degradation of CYP3A5 mRNA: a CYP3A5 minigene consisting of CYP3A5 exons and introns 3 to 6 transfected...

OBJECTIVES To assess the impact of the loss-of-function CYP3A5*3 allele (rs776746, 6986A>G SNP) on darunavir (DRV) plasma concentrations. METHODS 135 HIV-1 infected patients treated with DRV-based therapy were included in the study and plasma samples were obtained immediately before drug intake in order to determine DRV trough concentrations using an ultra performance liquid chromatography me...

A new CYP3A5 variant, CYP3A5*11, was found in a white European subject by DNA sequencing. The CYP3A5*11 allele contains a single nucleotide polymorphism (SNP) (g.3775A>G) in exon 2, which results in a Tyr53Cys substitution, and a g.6986A>G splice change, the latter SNP previously reported in the defective CYP3A5*3 allele. However, the CYP3A5*3 is not a null allele because this variant is associ...

The antipsychotic drug quetiapine is extensively metabolized by CYP3A4, but little is known about the possible influence of the polymorphic enzyme CYP3A5. This in vitro study investigated the relative importance of CYP3A4 and CYP3A5 in the metabolism of quetiapine and compared the metabolic pattern by the two enzymes, in the presence or absence of cytochrome b(5). Intrinsic clearance (CL(int)) ...

BACKGROUND The aim of our study was to determine the impact of CYP3A5*1 and CYP3A5*3 on the kinetics of tacrolimus in renal transplant recipients. MATERIAL AND METHODS Forty kidney recipients were selected to participate. Maintenance scheme consisted of tacrolimus, a purine inhibitor and a steroid. CYP3A5 genotyping was performed with PCR and RFLP. Pharmacokinetic model was developed with Lin...

To study mechanisms behind the interindividual variability in CYP3A expression and the relative contribution of the different CYP3A enzymes to the overall CYP3A activity, we have analyzed CYP3A4, CYP3A5, CYP3A43, and PXR mRNA and CYP3A4 and CYP3A5 protein expression, catalytic activity, and polymorphism in the CYP3A5 gene in a panel of 46 Caucasian human livers. Protein quantification was perfo...

A polymorphism in the cytochrome P450 3A CYP3A5 enzyme has been implicated in BP (blood pressure) control and arterial hypertension. Carriers of the CYP3A5*1 allele had high, whereas homozygous carriers of the CYP3A5*3 allele exhibit low, CYP3A5 expression in the kidney, where CYP3A5 represents the major CYP3A enzyme. The aim of the present study was to investigate the association of the CYP3A5...

CYP3A5 is a member of the CYP3A gene family which metabolizes 50% of therapeutic drugs and steroid hormones. CYP3A5*3 and CYP3A5*6 polymorphisms exhibit inter-individual differences in CYP3A5 expression. The CYP3A5*3 allele (A6986G transition in intron 3) results in loss of CYP3A5 expression and the CYP3A5*6 allele (G14690A transition in exon 2, leading to the skipping of exon 7) is associated ...

Recent research on CYP3A5 in vitro and in humans has provided discordant information on whether CYP3A5 plays a significant role in the metabolism of CYP3A substrates in vivo. For example, six separate studies have reported CYP3A5 to contribute between 2 and 60% of the total hepatic CYP3A. Suggested explanations for the reported differences in hepatic CYP3A5 levels are evaluated in this article....

Members of the cytochrome P450 3A (CYP3A) subfamily of drug metabolizing enzymes exhibit developmental changes in expression in human liver characterized by a transition between CYP3A7 and CYP3A4 over the first few years of life. In contrast, the developmental expression of CYP3A5 is less well understood due to polymorphic expression of the enzyme in human tissues as a result of the prevalence ...