Pharmacokinetics of Enalapril in Rats with Renal Impairment Induced by Adriamycin

Objective To investigate the effect of renal impairment on pharmacokinetics of enlaprilat, active metabolite of enalapril, angiotensin converting enzyme inhibitor, in rats. Methods A total of 16 rats were randomly divided into normal control group and renal impairment group induced by adriamycin, and then the rats were administrated with enalapril 20 mg/kg p.o. The plasma samples were gained, and the plasama concentration of enalaprilat, main metabolite of enalapril, was determined by HPLC-UV. Results After p.o. single dose enalapril 20 mg/kg, (Cmax)s of enalaprilat were 68.61 ±7.58 ng/ml for control group and 113.94 ±12.29 ng/ml for renal impairment group. Meantime, (tpeak)s were 3.35±0.82 h and 11.11±2.87 h,(t1/2)s were 10.74±2.32 h and 55.72±7.65 h,(AUC0-∞)s were 1.36±0.18 μg·ml-1·h-1 and 10.72±2.05 μg·ml-1·h-1, respectively, which showed statistical significance between 2 groups. Conclusion Renal impairment could prolong t1/2 significantly and augment the accumulation of enalapril. Therefore, it is important to correctly regulate the therapeutic scheme for using enalapril to treat renal impairment patients, especially, diabetic nephropathy.