Aweeka F, Gambertoglio J, Mills J, Jacobson M A
Division of Clinical Pharmacy, University of California, San Francisco 94143-0622.
Antimicrob Agents Chemother. 1989 May;33(5):742-5. doi: 10.1128/AAC.33.5.742.
Foscarnet has been shown to be active in vitro against the human immunodeficiency virus and all human herpesviruses including cytomegalovirus (CMV). A pharmacokinetic study was carried out as part of a clinical trial designed to evaluate the safety and efficacy of intermittently administered intravenous foscarnet for the treatment of CMV retinitis. Eight patients with acquired immunodeficiency syndrome and serious CMV retinitis received 2-h intravenous infusions of foscarnet at a dosage of 60 mg/kg of body weight every 8 h for 14 days. Serial plasma samples were collected on days 3 and 14 of therapy, and foscarnet concentrations were determined by high-pressure liquid chromatography. On day 3 of therapy, the mean (+/- standard deviation) peak and trough levels in plasma were 509 (200) and 98 (29) microM, respectively, while on day 14 levels were 495 (149) and 126 (59) microM. The mean clearance in plasma on days 3 and 14 were 1.9 (0.6) and 1.7 (0.9) ml/min per kg, respectively. On day 14, the mean half-life was 4.5 (1.2) h and the volume of distribution was 0.74 (0.60) liter/kg. As the half-life and the clearance of foscarnet in plasma correlated with changes in renal function, dosage adjustments must be made for patients with decreased renal function.
膦甲酸钠已被证明在体外对人类免疫缺陷病毒及所有人类疱疹病毒包括巨细胞病毒（CMV）具有活性。作为一项临床试验的一部分，开展了一项药代动力学研究，该试验旨在评估间歇性静脉注射膦甲酸钠治疗CMV视网膜炎的安全性和疗效。8例获得性免疫缺陷综合征且患有严重CMV视网膜炎的患者接受了膦甲酸钠静脉输注，剂量为60mg/kg体重，每8小时一次，共14天，每次输注2小时。在治疗的第3天和第14天采集系列血浆样本，采用高压液相色谱法测定膦甲酸钠浓度。治疗第3天，血浆中平均（±标准差）峰浓度和谷浓度分别为509（200）μM和98（29）μM，而在第14天，浓度分别为495（149）μM和126（59）μM。第3天和第14天血浆中的平均清除率分别为每千克体重1.9（0.6）和1.7（0.9）ml/min。在第14天，平均半衰期为4.5（1.2）小时，分布容积为0.74（0.60）升/千克。由于膦甲酸钠在血浆中的半衰期和清除率与肾功能变化相关，因此肾功能减退的患者必须调整剂量。
