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Disposition of pravastatin sodium, a tissue‐selective HMG‐CoA reductase inhibitor, in healthy subjects.
Author(s) -
Singhvi SM,
Pan HY,
Morrison RA,
Willard DA
Publication year - 1990
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1990.tb03626.x
Subject(s) - pravastatin , bioavailability , urine , hmg coa reductase , pharmacology , hydroxymethylglutaryl coa reductase , crossover study , volume of distribution , chemistry , pharmacokinetics , oral administration , sodium , reductase , endocrinology , medicine , cholesterol , biochemistry , enzyme , placebo , alternative medicine , organic chemistry , pathology
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.