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. 1990 The British Pharmacological Society