Boike S C, Pue M, Audet P R, Freed M I, Fairless A, Ilson B E, Zariffa N, Jorkasky D K
Department of Clinical Pharmacology, SmithKline Beecham Pharmaceuticals, Philadelphia, Pennsylvania 19104.
J Clin Pharmacol. 1994 Dec;34(12):1199-207. doi: 10.1002/j.1552-4604.1994.tb04732.x.
The pharmacokinetic profile of penciclovir was determined after a single 500-mg dose of its oral precursor, famciclovir, in 9 healthy volunteers and in 14 patients with chronic hepatic disease. Plasma and urine samples were analyzed for concentrations of penciclovir and 6-deoxy-penciclovir using a reverse-phase high-performance liquid chromatography (HPLC) method. Famciclovir was not quantifiable in patients with hepatic disease, and 6-deoxy-penciclovir was quantifiable in only a limited number of specimens. The extent of systemic availability of penciclovir, as measured by AUC0-infinity, was similar in patients with hepatic disease and in healthy subjects. In contrast, Cmax was significantly lower (average decrease of 43%) in subjects with hepatic disease relative to healthy normal subjects. Median Tmax for subjects with hepatic disease was significantly increased (by 0.75 hours) compared with subjects with normal liver function. These data suggest a decrease in the rate, but not the extent, of systemic availability of penciclovir in patients with hepatic disease. It should be unnecessary to modify the dose of famciclovir for subjects with compensated hepatic disease and normal renal function.
在9名健康志愿者和14名慢性肝病患者中，口服其前体药物泛昔洛韦单次剂量500毫克后，测定了喷昔洛韦的药代动力学特征。使用反相高效液相色谱（HPLC）法分析血浆和尿液样本中喷昔洛韦和6-脱氧喷昔洛韦的浓度。在肝病患者中无法检测到泛昔洛韦，仅在有限数量的样本中可检测到6-脱氧喷昔洛韦。以AUC0-∞衡量，喷昔洛韦在肝病患者和健康受试者中的全身可用性程度相似。相比之下，肝病患者的Cmax显著低于健康正常受试者（平均降低43%）。与肝功能正常的受试者相比，肝病患者的中位Tmax显著延长（延长0.75小时）。这些数据表明，肝病患者中喷昔洛韦的全身可用性速率降低，但程度未降低。对于肝功能代偿良好且肾功能正常的受试者，无需调整泛昔洛韦的剂量。
