Effects of cysteine on the pharmacokinetics of oltipraz in rats with protein-calorie malnutrition

Effects of cysteine on the pharmacokinetics of oltipraz were investigated after iv (10 mg/kg) and oral (30 mg/kg) administration to male control, protein-calorie malnutrition (PCM), and PCM with oral cysteine supplementation (PCMC) rats. It was reported that oltipraz was mainly metabolized via hepatic CYP1A1/2,2B1/2,2C11, 3A1/2, and 2D1 in male rats. The expression and mRNA levels of CYP1A2,2C11, and 3A1/2 were also reported to decrease in male PCM rats compared with controls. Interestingly, the decreased CYP isozymes in PCM rats returned fully or partially to controls by oral cysteine supplementation (PCMC rats). Hence, it would be expected that in PCM rats, some pharmacokinetic parameters of oltipraz are fully or partially returned to controls by cysteine. This was proven by the following parameters in PCMC rats: the AUC (328, 782, and 416 mu g min/mL for control, PCM, and PCMC rats, respectively, after iv administration, and 223, 456, and 242 mu g min/mL after oral administration), terminal half-life (130, 212, and 143 min), mean residence time (MRT) (149,299, and 189 min), and in vitro CLint (0.181, 0.107, and 0.153 mL/min/mg protein) were fully returned to controls, and CL and CLNR values were partially returned to controls. (c) 2005 Wiley-Liss,Inc. and the American Pharmacists Association.