de Miranda P, Krasny H C, Page D A, Elion G B
Am J Med. 1982 Jul 20;73(1A):31-5. doi: 10.1016/0002-9343(82)90059-6.
The disposition of acyclovir was investigated in several species. The drug was well distributed into all the tissues, including the brain, in mice and rats. Binding of acyclovir to plasma proteins was 36 percent or lower. After intravenous bolus dosing (20 mg/kg) in dogs, the plasma acyclovir concentration-time profile, determined by radioimmunoassay, showed a biphasic decline with a half-life in the elimination phase of 2.3 +/- 0.1 hours. The volume of distribution (Vd beta) of 1.2 +/- 0.2 liters/kg indicated distribution of drug into the tissues. Marked species differences were observed in the gastrointestinal absorption and biotransformation of acyclovir. Oral dosing produced better absorption in dogs and mice than in rats and rhesus monkeys. More than 95 percent of the radioactivity in the urine derived from a 14C-acyclovir parenteral dose was recovered as the unchanged drug in mice, rats, and dogs. Minor urinary metabolites were characterized by high-performance liquid chromatography as 9-carboxymethoxymethylguanine (CMMG) and 8-hydroxy-9-(2-hydroxyethoxymethyl)guanine. In other species--guinea pig, rabbit, and rhesus monkey--up to 40 percent of the radioactivity in the urine consisted of these metabolites.
在多个物种中对阿昔洛韦的处置情况进行了研究。在小鼠和大鼠体内，该药物能很好地分布到包括脑在内的所有组织中。阿昔洛韦与血浆蛋白的结合率为36%或更低。给犬静脉推注给药（20mg/kg）后，通过放射免疫分析法测定的血浆阿昔洛韦浓度-时间曲线呈双相下降，消除相半衰期为2.3±0.1小时。分布容积（Vdβ）为1.2±0.2升/千克，表明药物分布到了组织中。在阿昔洛韦的胃肠道吸收和生物转化方面观察到了明显的物种差异。口服给药在犬和小鼠中的吸收情况优于大鼠和恒河猴。在小鼠、大鼠和犬中，静脉注射14C-阿昔洛韦剂量后，尿液中超过95%的放射性以原形药物形式回收。通过高效液相色谱法鉴定出的少量尿液代谢产物为9-羧甲氧基甲基鸟嘌呤（CMMG）和8-羟基-9-（2-羟基乙氧基甲基）鸟嘌呤。在其他物种——豚鼠、兔和恒河猴中，尿液中高达40%的放射性由这些代谢产物组成。
