Dieterich D T, Poles M A, Lew E A, Martin-Munley S, Johnson J, Nix D, Faust M J
New York University Medical Center, New York, USA.
Antimicrob Agents Chemother. 1997 Jun;41(6):1226-30. doi: 10.1128/AAC.41.6.1226.
Ten patients with AIDS and cytomegalovirus (CMV) gastrointestinal infection were included in an open-label study to evaluate the safety, efficacy, and pharmacokinetics of 90 mg of intravenous foscarnet/kg of body weight twice daily accompanied by (pre)hydration of 500 to 750 ml. Efficacy was documented endoscopically, while safety was evaluated clinically by patient reports and physical and laboratory observation. The pharmacokinetics of foscarnet was evaluated after the first dose and following approximately 20 days of therapy. Nine patients (90%) responded histopathologically, nine (90%) responded endoscopically, and nine (90%) responded symptomatically to foscarnet therapy. Adverse events resulted in discontinuance of medication in the case of one patient. The mean maximal concentration was 621 microM following the first dose and 687 microM at steady state (P = 0.11). The apparent elimination rate constant and elimination half-life were not different between dose 1 and steady state. There were no significant changes in foscarnet excretion or renal clearance between dose 1 and steady state. The steady-state volume of distribution was 23.4 liters following the first dose and 19.0 liters at steady state (P < 0.002). Twice-daily foscarnet appeared to be safe and efficacious in the treatment of CMV gastrointestinal disease in this study, resulting in endoscopic or histologic improvement in 9 of the 10 (90%) patients. Minor changes in clearance and volume of distribution noted at steady state compared to single-dose administration are readily explained by study design, known information about foscarnet pharmacokinetics, and changes in body weight and creatinine clearance in the patients.
十名患有艾滋病和巨细胞病毒（CMV）胃肠道感染的患者被纳入一项开放标签研究，以评估每日两次静脉注射90毫克膦甲酸钠/千克体重并伴有500至750毫升（预）补液的安全性、疗效和药代动力学。通过内镜检查记录疗效，同时通过患者报告以及体格和实验室观察对安全性进行临床评估。在首剂给药后以及治疗约20天后评估膦甲酸钠的药代动力学。九名患者（90%）在组织病理学上有反应，九名（90%）在内镜检查中有反应，九名（90%）在症状方面对膦甲酸钠治疗有反应。一名患者因不良事件而停药。首剂给药后的平均最大浓度为621微摩尔，稳态时为687微摩尔（P = 0.11）。首剂与稳态时的表观消除速率常数和消除半衰期无差异。首剂与稳态时膦甲酸钠的排泄或肾脏清除率无显著变化。首剂给药后的稳态分布容积为23.4升，稳态时为19.0升（P < 0.002）。在本研究中，每日两次的膦甲酸钠治疗CMV胃肠道疾病似乎安全有效，10名患者中有9名（90%）在内镜或组织学上有改善。与单剂量给药相比，稳态时清除率和分布容积的微小变化可通过研究设计、膦甲酸钠药代动力学的已知信息以及患者体重和肌酐清除率的变化轻易解释。
