摘要：The stability of spironolactone (SPN) in rat plasma was studied and its degradation was found to be an apparent first-order reaction. The apparent first-order rate constants ( k obs) at 37, 23.5 and 0 °C were 3.543±0.261 (h−1, mean±S.D., n =3), 6.278±0.045 (×10−1 h−1), and 7.336±0.843 (×10−2 h−1), respectively. The half-lives were 0.20 h, 1.10 h, and 9.53 h. The degradation rate of SPN in rat plasma was markedly decreased when NaF, an esterase inhibitor, was added to the plasma, and the degradation was catalyzed by esterase in the plasma. These results indicated that not only plasma but also blood and serum samples in rat pharmacokinetic studies should be cooled to 0 °C, the temperature maintained, and treated as soon as possible. In pharmacokinetic studies reported previously, the temperature control of plasma, blood, and serum samples was not described. The pharmacokinetic study in rats after intravenous administration of SPN at 20 mg/kg was performed with strict temperature control of plasma and blood samples. The AUC , MRT , CL and Vd ss values (mean±S.E. of 4 rats) for SPN were 4100.8±212.9 ng h/ml, 0.29±0.01 h, 4915.7±248.0 ml/h/kg, and 1435.4±48.4 ml/kg, respectively. The AUC value was much larger than that previously reported. The AUC , MRT , C max and T max values (mean±S.E. of 4 rats) of canrenone, an active metabolite of SPN, after the administration of SPN were 4196.1±787.5 ng h/ml, 1.99±0.13 h, 1546.3±436.4 ng/ml and 1.0±0.0 h, respectively. This AUC value was almost identical to the value previously reported.
