抗病毒核苷酸类似物9-(2-膦酰甲氧基乙基)腺嘌呤在食蟹猴中的口服、皮下和肌肉注射生物利用度。
Oral, subcutaneous, and intramuscular bioavailabilities of the antiviral nucleotide analog 9-(2-phosphonylmethoxyethyl) adenine in cynomolgus monkeys.
作者信息
Cundy K C, Shaw J P, Lee W A
机构信息
Gilead Sciences, Inc., Foster City, California 94404.
出版信息
Antimicrob Agents Chemother. 1994 Feb;38(2):365-8. doi: 10.1128/AAC.38.2.365.
Abstract
Intravenous, subcutaneous, intramuscular, and oral pharmacokinetics of the antiretroviral nucleotide analog [9-(2-phosphonylmethoxyethyl)adenine] (PMEA) were examined in a crossover study with four cynomolgus monkeys using 14C-labelled drug at 10 mg/kg of body weight (20 microCi/kg). Plasma radioactivity declined biexponentially following intravenous administration. Radiochromatography of plasma revealed an absence of PMEA metabolites. Intramuscular and subcutaneous bioavailabilities of PMEA were (means +/- standard deviation) 126% +/- 30% and 101% +/- 25%, respectively, supporting the clinical utility of these routes. The oral bioavailability of PMEA in this species (4.0% +/- 1.0%) appeared to be limited by intestinal permeability and is likely to be equally low in humans.
摘要
在一项交叉研究中，对4只食蟹猴静脉注射、皮下注射、肌肉注射和口服抗逆转录病毒核苷酸类似物9-(2-膦酰甲氧基乙基)腺嘌呤的药代动力学进行了研究，使用14C标记的药物，剂量为10mg/kg体重(20μCi/kg)。静脉给药后，血浆放射性呈双指数下降。血浆放射性色谱分析显示不存在PMEA代谢物。PMEA的肌肉注射和皮下注射生物利用度分别为(平均值±标准差)126%±30%和101%±25%，支持了这些给药途径的临床实用性。该物种中PMEA的口服生物利用度(4.0%±1.0%)似乎受肠道通透性限制，在人类中可能同样较低。
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