使用安替比林和硝苯地平“鸡尾酒”法研究肾衰竭对高血压患者细胞色素P450活性的影响

Influence of renal failure on cytochrome P450 activity in hypertensive patients using a "cocktail" of antipyrine and nifedipine.

作者信息

Lanchote V L, Ping W C, Santos S R

机构信息

Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Brazil.

出版信息

Eur J Clin Pharmacol. 1996;50(1-2):83-9. doi: 10.1007/s002280050073.

DOI:10.1007/s002280050073

PMID:8739816

Abstract

OBJECTIVE

Two substrates were coadministered in a "cocktail" approach to evaluate the contribution of renal failure to drug oxidation.

PATIENTS

Nineteen hypertensive patients, nine of them with chronic renal failure (CLCR 38.9 vs 102.3 ml.min-1 1.73 m-2), were investigated after peroral administration of a combination of antipyrine (500 mg, in capsules) and nifedipine (10 mg, in Oxcord capsules) in the morning after an overnight fast.

RESULTS

This "cocktail" approach made it possible to characterize in vivo the activities of different forms of cytochrome P450 in a single-study protocol using the total clearance of nifedipine and clearance for production of 3-hydroxymethylantipyrine (HMA), 4-hydroxyantipyrine (OHA) and norantipyrine (NORA). With this "cocktail" approach (antipyrine plus nifedipine), we can suggest a selective effect on the activities of cytochrome P450 forms associated with the formation of dehydronifedipine (P450 III A4) and of NORA in patients with mild renal failure under long-term antihypertensive therapy.

摘要

目的

采用“鸡尾酒”法同时给予两种底物，以评估肾衰竭对药物氧化的影响。

患者

19例高血压患者，其中9例患有慢性肾衰竭（肌酐清除率分别为38.9与102.3 ml·min⁻¹/1.73 m²），在空腹过夜后的早晨口服安替比林（500 mg，胶囊剂）和硝苯地平（10 mg，控释胶囊剂）的组合后进行研究。

结果

这种“鸡尾酒”法能够在单一研究方案中，通过硝苯地平的总清除率以及3-羟甲基安替比林（HMA）、4-羟基安替比林（OHA）和去甲安替比林（NORA）生成的清除率，对不同形式细胞色素P450的体内活性进行表征。采用这种“鸡尾酒”法（安替比林加硝苯地平），我们可以提示在长期抗高血压治疗下，对轻度肾衰竭患者中与脱氢硝苯地平（P450 III A4）形成及NORA相关的细胞色素P450形式的活性有选择性影响。