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.
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.
Lake-Bakaar
D M
DM
Department of Antiviral Therapy, Research & Development, Astra Alab AB, Södertälje, Sweden.
Lindborg
B
B
Datema
R
R
D000042:Absorption; D000284:Administration, Oral; D000818:Animals; D000998:Antiviral Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D004952:Esters; D006147:Guanine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D014645:Herpesvirus 3, Human / Q000187:drug effects*; D008252:Macaca fascicularis; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012492:Salts
D000998:Antiviral Agents; D004952:Esters; D012492:Salts; C051755:9-(4-hydroxy-2-(hydroxymethyl)butyl)guanine; D006147:Guanine