Characterization of hepatic cytochrome P4503A activity in patients with end-stage renal disease
Characterization of hepatic cytochrome P4503A activity in patients with end-stage renal disease
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DOI：
10.1016/s0009-9236(03)00056-0
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发表时间：
2003-05-01
影响因子：
6.7
通讯作者：
Henrich, WL
中科院分区：
文献类型：
--
作者：
Dowling, TC;Briglia, AE;Henrich, WL
背景资料：细胞色素P450（CYP 450）氧化酶系统主要位于肝脏和小肠，负责许多内源性和外源性物质的代谢和解毒。最丰富的酶，CYP 3A，已知参与200多种常用药物的代谢。在肾衰竭的实验模型中，肝功能和肌酐酶含量均降低;然而，缺乏人体的直接证据。终末期肾病患者的药物代谢的评价是很重要的，因为这些患者使用大量的药物，并在不良反应和药物-药物interactions.Methods的风险：我们测量了肝脏CYP 3A活性在基线和利福平（国际非专利药品，利福平）酶诱导后，在12例终末期肾病和12名健康，年龄匹配的对照。用红霉素呼气试验表征肝脏CYP 3A表型，用短期利福平评价酶诱导能力结果：终末期肾病组基线红霉素呼气试验值比对照组低28（P < .05）;然而，利福平给药后的酶诱导能力在组间相似结论：终末期肾病患者药物毒性风险增加的机制之一是CYP 3A酶途径活性降低。(Clin Pharmacol Ther 2003;73：427-34.）。
Background: The cytochrome P450 (CYP) oxidative enzyme system, located primarily in the liver and small intestine, is responsible for metabolism and detoxification of numerous endogenous and exogenous substances. The most abundant CYP enzyme, CYP3A, is known to be involved in the metabolism of more than 200 commonly used medications. In experimental models of renal failure, both hepatic function and CYP enzyme content are reduced; however, direct evidence in humans is lacking. Evaluation of drug metabolism in patients with end-stage renal disease is important because these patients use a large number of medications and are at risk of adverse reactions and drug-drug interactions.Methods: We measured hepatic CYP3A activity at baseline and after rifampin (INN, rifampicin) enzyme induction in 12 patients with end-stage renal disease and 12 healthy, age-matched controls. Hepatic CYP3A phenotype was characterized with the erythromycin breath test, and enzyme induction capacity was evaluated with a short course of rifampin (600 mg/d for 6 days).Results: The end-stage renal disease group had 28% lower baseline erythromycin breath test values than controls (P < .05); however, enzyme induction capacity after rifampin administration was similar between groups (P = .70).Conclusion: The findings suggested that one mechanism by which patients with end-stage renal disease are at increased risk of drug toxicity is reduced activity of the CYP3A enzyme pathway. (Clin Pharmacol Ther 2003;73:427-34.).