Lake-Bakaar D M, Lindborg B, Datema R
Department of Antiviral Therapy, Research & Development, Astra Alab AB, Södertälje, Sweden.
Antimicrob Agents Chemother. 1989 Jan;33(1):110-2. doi: 10.1128/AAC.33.1.110.
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.
为提高（R,S）-9-[4-羟基-2-（羟甲基）丁基]鸟嘌呤[（±）2HM-HBG]的胃肠道吸收，合成了该化合物的各种盐和酯，并在大鼠和猴子身上进行了药代动力学实验。（±）2HM-HBG的钠盐或盐酸盐以及短链酯的生物利用度特征与（±）2HM-HBG一样差。然而，以盐形式给药的酯比母体化合物更容易被吸收。6-脱氧和6-脱氧二乙酸酯类似物在体内被广泛氧化，是具有提高口服（±）2HM-HBG吸收的巨大潜力的前药。
