Pharmacokinetics and oral bioavailability of pravastatin in dogs

• Published in: International journal of pharmaceutics Vol. 143; no. 2; pp. 265 - 269
• Main Authors: Morrison, Richard A., Singhvi, Sampat M.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 08.11.1996; Elsevier
• Subjects: Biological and medical sciences; Dogs; General and cellular metabolism. Vitamins; Intravenous; Medical sciences; Oral; Pharmacokinetics; Pharmacology. Drug treatments; Pravastatin; Oral; Pharmacokinetics; Pravastatin; Intravenous; Dogs; Human; Fissipedia; Animal model; Carnivora; Enzyme; Interspecific comparison; Oral administration; Enzyme inhibitor; Bioavailability; Assay; Vertebrata; Mammalia; Animal; Hydroxymethylglutaryl-CoA reductase; Oxidoreductases; Dog; Antilipemic agent
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/S0378-5173(96)04714-X

Pravastatin sodium, an antihypercholesterolemic HMG-CoA reductase inhibitor, has recently been shown to significantly reduce the incidence of myocardial infarction and death from cardiovascular causes, without adversely affecting the risk of death from non-cardiovascular causes in men with moderate hypercholesterolemia. Because the dog is used as an animal model for pharmacology/toxicology studies, a pharmacokinetic study was carried out in dogs to provide the basis for interspecies comparisons to humans and also to guide dosage selection, so as to provide clinically-relevant exposure in the dog. Values for total body clearance, renal clearance, elimination t 1 2 , and oral bioavailability of pravastatin in dogs are different than those in humans. Based on observed systemic exposure of pravastatin in dogs and literature values for humans, there is approximately a 2.6-fold greater exposure in dogs than in humans at equivalent oral doses.