Metabolism and pharmacokinetics of a double prodrug of ganciclovir in the rat and monkey.
Drug Metab Dispos
; 23(11): 1242-7, 1995 Nov.
Article
en En
| MEDLINE
| ID: mdl-8591725
Ganciclovir (GCV), which is used in the treatment of human cytomegalovirus infections, is poorly absorbed orally. A double prodrug of GCV, the dipivalate ester of 6-deoxy-GCV (6-dGCV) (called 6-dGCV-DPiv), was given orally to rats (25 mg/kg) and resulted in a nearly 7-fold enhancement of GCV bioavailability compared with administration of GCV alone and a 2-fold increase compared with administration of 6-dGCV. The prodrug was rapidly hydrolyzed and extensively oxidized by first-pass metabolism in such a way that only GCV, 6-dGCV, and a small amount of the monopivalate ester of 6-dGCV were observed in rat plasma. In cynomolgus monkey was given the prodrug orally (22.5 mg/kg), two additional metabolites were observed--the 8-hydroxy analogs of GCV and dGCV. The double prodrug approach demonstrated the potential for enhanced oral delivery of GCV in humans.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Antivirales
/
Profármacos
/
Ganciclovir
Límite:
Animals
Idioma:
En
Revista:
Drug Metab Dispos
Asunto de la revista:
FARMACOLOGIA
Año:
1995
Tipo del documento:
Article
Pais de publicación:
Estados Unidos