Fletcher C, Sawchuk R, Chinnock B, de Miranda P, Balfour H H
Clin Pharmacol Ther. 1986 Sep;40(3):281-6. doi: 10.1038/clpt.1986.177.
The pharmacokinetics of the antiviral drug 9-[2-hydroxy-1-(hydroxymethyl) ethoxymethyl]guanine (DHPG) were examined in six patients receiving 2.5 or 5.0 mg/kg every 8 or 12 hours for human cytomegalovirus (HCMV) pneumonitis or retinitis. Biexponential decay with a mean distribution t1/2 of 0.23 hours and terminal t1/2 of 2.53 hours was observed. Total clearance correlated well with and exceeded creatinine clearance by a factor of 2.4. Mean volume of the central compartment was 15.26 L/1.73 m2 and the volume of distribution at steady state was 32.8 L/1.73 m2. Peak (model predicted) and trough plasma concentrations were 4.75 to 6.20 micrograms/ml and less than 0.25 to 0.63 microgram/ml, respectively, in patients receiving 2.5 mg/kg. Peak concentrations are well above those needed to inhibit HCMV at the 50% level (ID50) and troughs are near this ID50. Cerebrospinal fluid concentrations of DHPG indicate a penetration of 24% to 67%. No accumulation of DHPG was apparent in these patients. However, dosage reduction is necessary in renal insufficiency. Neutropenia occurred in one patient. The plasma concentration profile of DHPG suggests potential beneficial activity against HCMV.
对6例因人类巨细胞病毒（HCMV）肺炎或视网膜炎而每8或12小时接受2.5或5.0mg/kg剂量的抗病毒药物9-[2-羟基-1-（羟甲基）乙氧基甲基]鸟嘌呤（DHPG）的患者进行了药代动力学研究。观察到双指数衰减，平均分布半衰期为0.23小时，终末半衰期为2.53小时。总清除率与肌酐清除率相关性良好，且超出肌酐清除率2.4倍。中央室平均容积为15.26L/1.73m²，稳态分布容积为32.8L/1.73m²。接受2.5mg/kg剂量的患者中，（模型预测的）峰浓度和谷浓度分别为4.75至6.20μg/ml和低于0.25至0.63μg/ml。峰浓度远高于抑制HCMV 50%水平（ID50）所需浓度，谷浓度接近该ID50。DHPG的脑脊液浓度表明其穿透率为24%至67%。这些患者中未出现DHPG蓄积。然而，肾功能不全时需要减少剂量。1例患者出现中性粒细胞减少。DHPG的血浆浓度曲线表明其对HCMV可能具有有益活性。
