Chatelut E, Rostaing L, Grégoire N, Payen J L, Pujol A, Izopet J, Houin G, Canal P
Institut Claudius-Regaud, Centre Hospitalier Universitaire, Toulouse, France.
Br J Clin Pharmacol. 1999 Apr;47(4):365-71. doi: 10.1046/j.1365-2125.1999.00912.x.
To model the pharmacokinetic profiles of alpha interferon (alphaIFN) after a single subcutaneous (s.c.) injection of 3 million units of alpha 2b interferon, to correlate the pharmacokinetic parameters with patient demographic covariates, and to develop a limiting sampling strategy for determining the alphaIFN plasma area under the curve of concentration vs time (AUC).
The plasma alphaIFN pharmacokinetics were determined in 27 patients with chronic hepatitis C virus infection after the first s.c. injection of the drug. Ten patients had normal renal function and 17 were chronic haemodialysis patients. Plasma samples were assayed by an Elisa method. Concentration-time data was analysed by a population approach using NONMEM.
The pharmacokinetic model which better described the concentration vs time data was a one-compartment model with two processes of absorption: a zero-order followed by a first-order process. The mean clearance of dialysis patients represented 37% (with 95% confidence interval: 30% -44%) of the mean value of the patients with normal renal function. The volume of distribution was significantly correlated to the body surface area. Bayesian analysis using NONMEM allowed determination of the individual plasma AUC from three samples within the 24 h period post s.c. injection.
The present pharmacokinetic model will allow one to obtain individual parameters such as, the area under the curve of concentration vs time from a limited-sampling strategy, and to perform pharmacokinetic-pharmacodynamic analysis of combined alphaIFN plasma concentrations and viraemic data.
对单次皮下注射300万单位α2b干扰素后α干扰素（αIFN）的药代动力学特征进行建模，将药代动力学参数与患者人口统计学协变量相关联，并制定一种有限采样策略以确定αIFN血浆浓度-时间曲线下面积（AUC）。
在27例慢性丙型肝炎病毒感染患者首次皮下注射该药物后测定血浆αIFN药代动力学。10例患者肾功能正常，17例为慢性血液透析患者。采用酶联免疫吸附测定法（ELISA法）检测血浆样本。使用非线性混合效应模型（NONMEM）通过群体方法分析浓度-时间数据。
能更好地描述浓度-时间数据的药代动力学模型是具有两个吸收过程的单室模型：零级过程后接一级过程。透析患者的平均清除率为肾功能正常患者平均值的37%（95%置信区间：30% - 44%）。分布容积与体表面积显著相关。使用NONMEM进行贝叶斯分析可根据皮下注射后24小时内的三个样本确定个体血浆AUC。
当前的药代动力学模型将使人们能够从有限采样策略中获得个体参数，如浓度-时间曲线下面积，并对αIFN血浆浓度和病毒血症数据进行药代动力学-药效学分析。
