Improvement of the absorption of oral (R,S)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine, an anti-varicella-zoster virus drug, in rats and monkeys.

AUTOR(ES)

Lake-Bakaar, D M

RESUMO

In an effort to improve the gastrointestinal absorption of (R,S)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine [(+/-)2HM-HBG], various salts and esters of the compound were synthesized and pharmacokinetic experiments were performed in rats and monkeys. The sodium or hydrochloride salts and short-chain esters of (+/-)2HM-HBG showed bioavailability characteristics that were equally as poor as those of (+/-)2HM-HBG. However, the esters given as salts tended to be better absorbed than the parent compound. The 6-deoxy and 6-deoxydiacetate analogs were extensively oxidized in vivo and represent prodrugs with considerable potential in improving the absorption of oral (+/-)2HM-HBG.

Documentos Relacionados

• Pharmacokinetics and antiviral activity in simian varicella virus-infected monkeys of (R,S)-9-[4-hydroxy-2-(hydroxymethyl) butyl]guanine, an anti-varicella-zoster virus drug.
• Inhibiting effect of (RS)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine on varicella-zoster virus replication in cell culture.
• Efficacy of (-)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine in African green monkeys infected with simian varicella virus.
• Mode of action of (R)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine against herpesviruses.
• Inhibition of varicella-zoster virus-induced DNA polymerase by a new guanosine analog, 9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine triphosphate.