Jullien Vincent, Urien Saïk, Chappuy Hélène, Dimet Jérôme, Rey Elisabeth, Pons Gérard, Blanche Stéphane, Tréluyer Jean-Marc
Pharmacologie Clinique, Université René Descartes, Groupe Hospitalier Cochin-Saint-Vincent-de-Paul, Assistance Publique-Hôpitaux de Paris, 82 Avenue Denfert-Rochereau, 75674 Paris Cedex 14, France.
J Clin Pharmacol. 2005 Mar;45(3):257-64. doi: 10.1177/0091270004272215.
Abacavir pharmacokinetics was studied in 105 children by a population approach performed with NONMEM. A 1-compartment open model with linear absorption and elimination adequately described the data. Typical population estimates (percent interindividual variability) of absorption rate constant, apparent distribution volume, and apparent plasma clearance were 1.79 h(-1) (58%), 42.9 L (53%), and 24.3 L/h (30%), respectively. Apparent plasma clearance was positively related to body weight. Individual Bayesian estimates of apparent plasma clearance were used to calculate individual abacavir area under the concentration curve (AUC). For the current weight-based regimen, abacavir exposure was found to be constant throughout the age range of the study, with an overall mean AUC value of 8.5 +/- 2.5 mg x h/L, which is slightly greater than the mean AUC value reported in adults. This study confirms the relevance of the current weight-based abacavir dosage regimen in pediatric patients.
采用NONMEM群体方法对105名儿童的阿巴卡韦药代动力学进行了研究。具有线性吸收和消除的一室开放模型能充分描述数据。吸收速率常数、表观分布容积和表观血浆清除率的典型群体估计值(个体间变异性百分比)分别为每小时1.79(58%)、42.9升(53%)和每小时24.3升(30%)。表观血浆清除率与体重呈正相关。表观血浆清除率的个体贝叶斯估计值用于计算阿巴卡韦的个体血药浓度曲线下面积(AUC)。对于当前基于体重的给药方案,发现在研究的整个年龄范围内阿巴卡韦的暴露量是恒定的,总体平均AUC值为8.5±2.5毫克·小时/升略高于成人报告中的平均AUC值。本研究证实了当前基于体重的阿巴卡韦给药方案在儿科患者中的相关性。