Taburet A M, Katlama C, Blanshard C, Zorza G, Gazzard D, Dohin E, Gazzard B G, Frostegard C, Singlas E
Hôpital Universitaire Bicêtre, Le Kremlin Bicêtre, France.
Antimicrob Agents Chemother. 1992 Sep;36(9):1821-4. doi: 10.1128/AAC.36.9.1821.
The pharmacokinetics of foscarnet were evaluated in 11 AIDS patients with cytomegalovirus disease after twice-daily infusion of 90 mg/kg of body weight for 2 weeks. All patients were hydrated during foscarnet infusion. Blood and urine samples were collected on days 1, 7, and 14 of therapy. Foscarnet concentrations were measured by high-pressure liquid chromatography. Despite large interindividual variations, no significant differences were seen between day 1, day 7, and day 14 concentrations in plasma. Mean peak and trough concentrations on day 14 of therapy were 605 +/- 118 and 52 +/- 59 microM, respectively. In all patients, peak concentrations were well above those necessary to inhibit cytomegalovirus. Pharmacokinetic parameters remained stable throughout the study. On day 14, the mean half-life was 3.4 h, total and renal clearances were 118 and 92 ml/min, respectively, and the volume of distribution was 0.6 liter/kg. These data and previous clinical trials demonstrate that this more convenient dosage regimen can be safely used for patients with cytomegalovirus disease. The side effects were comparable to those reported with other dosage regimens, although no renal impairment was seen in this study, probably because of the hydration.
对11例患有巨细胞病毒疾病的艾滋病患者进行了膦甲酸钠的药代动力学评估,这些患者每天两次静脉输注90mg/kg体重,持续2周。在输注膦甲酸钠期间,所有患者均进行了补液。在治疗的第1天、第7天和第14天采集血液和尿液样本。通过高压液相色谱法测量膦甲酸钠浓度。尽管个体间差异较大,但血浆中第1天、第7天和第14天的浓度未见显著差异。治疗第14天的平均峰浓度和谷浓度分别为605±118μM和52±59μM。在所有患者中,峰浓度远高于抑制巨细胞病毒所需的浓度。在整个研究过程中,药代动力学参数保持稳定。第14天,平均半衰期为3.4小时,总清除率和肾清除率分别为118和92ml/min,分布容积为0.6升/千克。这些数据和先前的临床试验表明,这种更方便的给药方案可安全用于巨细胞病毒疾病患者。副作用与其他给药方案报道的副作用相当,尽管本研究中未见肾功能损害,可能是因为进行了补液。