Open AccessImprovement of the absorption of oral (R,S)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine, an anti-varicella-zoster virus drug, in rats and monkeys
Author(s) -
Desmond M. LakeBakaar,
B Lindborg,
Roelf Datema
Publication year - 1989
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.33.1.110
Subject(s) - hydroxymethyl , prodrug , guanine , bioavailability , absorption (acoustics) , hydrochloride , pharmacokinetics , chemistry , in vivo , drug , pharmacology , oral administration , stereochemistry , medicine , biochemistry , biology , nucleotide , physics , microbiology and biotechnology , acoustics , gene
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.