Comparison of Plasma Profiles of Lovastatin (Mevinolin), Simvastatin (Epistatin) and Pravastatin (Eptastatin) in the Dog

Autor: R. J. Gerson, W.F. Bayne, M. S. Schwartz, T. J. Thornton, R.J. Stubbs
Rok vydání: 1990
Předmět:
Zdroj: Drug Investigation. 2:18-28
ISSN: 1179-1918
0114-2402
DOI: 10.1007/bf03258190
Popis: Lovastatin (mevinolin) [LV], simvastatin (epistatin) [SV] and pravastatin (eptastatin) [PVA] are indicated in the treatment of hypercholesterolaemia and are potent inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase. Beagle dogs were dosed orally with LV and SV (both lactones), PVA (a hydroxy acid), LVA (the β-hydroxy acid of LV) and SVA (the β-hydroxy acid of SV), in separate experiments. Measurement of enzyme inhibitory activities showed that the plasma concentrations were considerably higher after dosing with the hydroxy acids LVA, SVA and PVA than after the lactones LV and SV, for equivalent doses. Plasma samples were also assayed for active metabolites by a specific high performance liquid chromatography (HPLC) method; these were LVA and SVA, together with their 6′-β-hydroxy, 6′-β-hydroxymethyl, and 6′-exomethylene analogues. These metabolites were present in roughly equal concentrations after dosing with the lactones LV and SV. The unchanged drug was the major component after dosing with the hydroxy acids LVA, SVA and PVA. The major metabolite present after dosing with LVA and SVA was the 6′-exomethylene analogue. This work demonstrates a basic difference in plasma concentrations and metabolic profiles between the lactones LV and SV and the hydroxy acids LVA, SVA and PVA after oral administration to the dog.
Databáze: OpenAIRE
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