Disposition of pravastatin sodium, a tissue-selective HMG-CoA reductase inhibitor, in healthy subjects.
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.
Singhvi
S M
SM
Department of Drug Metabolism, Squibb Institute for Medical Research, Princeton, NJ 08540.
Pan
H Y
HY
Morrison
R A
RA
Willard
D A
DA
D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D002855:Chromatography, Thin Layer; D005243:Feces / Q000032:analysis; D006538:Heptanoic Acids / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007275:Injections, Intravenous; D009281:Naphthalenes / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D017035:Pravastatin; D011897:Random Allocation
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009281:Naphthalenes; D017035:Pravastatin