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

Effects of cysteine on the pharmacokinetics of torasemide were investigated after intravenous administration at a dose of 2 mg/kg to control rats and rats with PCM and PCMC. Torasemide was reported to be mainly metabolized via hepatic CYP2C9 in humans, and human CYP2C9 and male rat CYP2C11 proteins have 77% homology. It has also been reported that in male rats with PCM, the CYP2C11 level decreased to similar to20% of the control level, but the decreased CYP2C11 level in rats with PCM partially returned to the control level by oral cysteine supplementation (rats with PCMC. Hence, it could be expected that in rats with PCM, some pharmacokinetic parameters of torasemide could be significantly different compared with those in control rats and rats with PCMC; however, they could be not significantly different between control rats and rats with PCMC. This was proven by the following parameters; the AUC (1880, 4080, and 2290 mug (.) min/mL for control rats and rats with PCM and PCMC, respectively), terminal half-life (188, 277, and 139 min), MRT (154, 323, and 155 min), CL (1.06, 0.491, and 0.943 mL/min/kg), CLNR (0.992, 0.430, and 0.874 mL/min/kg), and in vitro intrinsic torasemide disappearance clearance, CLint (0.102, 0.0842, and 0.0997 mL/min/mg protein). (C) 2004 Wiley-Liss, Inc. and the American Pharmacists Association.