Singhvi S M, Pan H Y, Morrison R A, Willard D A
Department of Drug Metabolism, Squibb Institute for Medical Research, Princeton, NJ 08540.
Br J Clin Pharmacol. 1990 Feb;29(2):239-43. doi: 10.1111/j.1365-2125.1990.tb03626.x.
Pravastatin sodium, a competitive inhibitor of HMG-CoA reductase, is a new orally effective hypocholesterolaemic agent. In a two-way crossover study, eight healthy male subjects each received an intravenous and an oral dose of [14C]-pravastatin sodium. The oral absorption of [14C] activity from pravastatin sodium was about 34% and the oral bioavailability was about 18%, suggesting first-pass metabolism of pravastatin. After the intravenous dose, the recovery of radioactivity averaged 60% and 34% in urine and faeces, respectively. Corresponding values were 20% (urine) and 71% (faeces) for the oral dose. The estimated average plasma elimination half-life of pravastatin was 0.8 and 1.8 h for the intravenous and oral routes, respectively. The average values for total and renal clearances were 13.5 and 6.3 ml min-1 kg-1, respectively, and the steady-state volume of distribution averaged 0.51 kg-1. These results suggest that both kidney and liver are important sites of elimination for pravastatin.
普伐他汀钠是一种HMG-CoA还原酶的竞争性抑制剂，是一种新型口服有效的降胆固醇药物。在一项双向交叉研究中，8名健康男性受试者每人接受了静脉注射和口服剂量的[14C] - 普伐他汀钠。普伐他汀钠中[14C]活性的口服吸收率约为34%，口服生物利用度约为18%，提示普伐他汀存在首过代谢。静脉给药后，尿液和粪便中放射性的回收率分别平均为60%和34%。口服给药时相应的值分别为20%（尿液）和71%（粪便）。普伐他汀的估计平均血浆消除半衰期静脉给药和口服给药分别为0.8小时和1.8小时。总清除率和肾清除率的平均值分别为13.5和6.3 ml min-1 kg-1，稳态分布容积平均为0.51 kg-1。这些结果提示肾脏和肝脏都是普伐他汀的重要消除部位。
