Effects of the CYP3A5 genetic polymorphism on the pharmacokinetics of diltiazem.
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Yamamoto T, Kubota T, Ozeki T, Sawada M, Yokota S, Yamada Y, Kumagai Y, Iga T
Effects of the CYP3A5 genetic polymorphism on the pharmacokinetics of diltiazem.
Clin Chim Acta. 2005 Dec;362(1-2):147-54. doi: 10.1016/j.cccn.2005.06.013. Epub 2005 Jul 15.
- PubMed ID
- 16024008 [ View in PubMed]
- Abstract
BACKGROUND: The cytochrome P450 (CYP) 3A subfamily plays an important role in the metabolism of various endogenous and exogenous compounds. Among CYP3A subfamily members, CYP3A5 is polymorphically expressed and the CYP3A5*3 and CYP3A5*6 alleles are known not to express functional CYP3A5. Thus, these mutant alleles are thought to be responsible for interindividual variability of CYP3A activity. METHODS: Subjects possessing CYP3A5*1/*1, *1/*3 or *3/*3 received oral administration of diltiazem hydrochloride (60 mg), and plasma and urinary concentrations of diltiazem and its metabolite N-desmethyldiltiazem were measured. Before drug intake, cortisol metabolic clearance in each subject was measured to estimate in vivo CYP3A4 activity. RESULTS: The mean values of total oral diltiazem clearance of subjects with *1/*1, *1/*3 and *3/*3 were 183.4 +/- 39.4, 197.9 +/- 49.6 and 293.6 +/- 141.1 (l/h), respectively, and were not significantly different among the 3 genotype groups. The cortisol metabolic clearance was not significantly different among the three genotype groups, indicating that the CYP3A4 activity is not significantly different. CONCLUSION: The results suggest that CYP3A5*3 has only a minor effect on the pharmacokinetics and metabolism of diltiazem. Although our results did not indicate significance of CYP3A5, the effects of CYP3A5*3 on the metabolism of other CYP3A substrates remain to be investigated.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Diltiazem Cytochrome P450 3A5 Protein Humans UnknownSubstrateInhibitorDetails