期刊
DRUG METABOLISM AND DISPOSITION
卷 36, 期 8, 页码 1465-1469出版社
AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
DOI: 10.1124/dmd.107.020065
关键词
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资金
- NCRR NIH HHS [RR00046, M01 RR000046, M01 RR000046-441270, M01 RR000046-441267] Funding Source: Medline
- NICHD NIH HHS [5U10 HD045962-03, U10 HD045962] Funding Source: Medline
- NIGMS NIH HHS [U01 GM061393, U01 GM61374, U01 GM61393, U01 GM061374] Funding Source: Medline
The CYP3A5*1 allele has been associated with differences in the metabolism of some CYP3A substrates. CYP3A5 polymorphism may also influence susceptibility for certain drug interactions. We have previously noted a correlation between basal CYP3A activity and the inductive effects of dexamethasone using the erythromycin breath test (ERBT). To determine whether CYP3A5 polymorphism influences induction of CYP3A activity, we examined the effect of an antiemetic regimen of dexamethasone, and the prototypical inducer rifampin, on the ERBT in African American volunteers prospectively stratified by CYP3A5*1 allele carrier status. Mean basal ERBTs were significantly higher in CYP3A5*1 carriers (2.71 +/- 0.53%) versus noncarriers (2.12 +/- 0.37%, P = 0.006). Rifampin increased ERBTs in CYP3A5*1 carriers (4.68 versus 2.60%, P = 0.0008) and noncarriers (3.55 versus 2.11%, P = 0.0017), whereas dexamethasone increased ERBTs only in CYP3A5*1 noncarriers (3.03 versus 2.14%, P = 0.031). CYP3A5 polymorphism appears to influence susceptibility to induction-type drug interactions for some inducers, and CYP3A5*1 noncarriers may be more susceptible to the inductive effects of dexamethasone as a result of lower basal CYP3A activity.
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