INHIBITION OF RAT HEPATIC MITOCHONDRIAL ALDEHYDE DEHYDROGENASE ISOZYMES BY REPEATED CYANAMIDE ADMINISTRATION - PHARMACOKINETIC-PHARMACODYNAMIC RELATIONSHIPS

被引：1

作者：

PIERA, JP ^{[1
]}

OBACH, R ^{[1
]}

SAGRISTA, ML ^{[1
]}

BOZAL, J ^{[1
]}

机构：

[1] UNIV BARCELONA,FAC PHARM,DEPT PHARM,E-08028 BARCELONA,SPAIN

来源：

BIOPHARMACEUTICS & DRUG DISPOSITION | 1993年 / 14卷 / 05期

关键词：

CYANAMIDE; RAT; LIVER; MITOCHONDRIAL; ALDEHYDE; DEHYDROGENASE; ISOZYMES INHIBITION;

D O I：

10.1002/bdd.2510140508

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The inhibition of rat hepatic mitochondrial aldehyde dehydrogenase (ALDH) isozymes was studied in apparent steady-state conditions after repeated intra-peritoneal cyanamide administration. The low-K(m) mitochondrial ALDH isozyme was more susceptible to cyanamide-induced inhibition (DI50 = 0.104 mg kg-1) than the high-K(m) isozyme (DI50 = 8.52 mg kg-1), with almost complete inhibition occurring at 0.35 mg kg-1 total cyanamide administered for the low-K(m) isozyme. The relationships between plasma and liver cyanamide concentrations and the inhibition of high-K(m) ALDH were established by means of the sigmoid I(max) model. The effect of dosing rate on the plasma concentration of cyanamide at apparent steady-state showed non-linearity, indicating that clearance or first-pass metabolism of cyanamide during its absorption after intraperitoneal administration did not remain constant throughout the range of doses studied.

引用

页码：419 / 428

页数：10