Martin E S, Crismon M L, Godley P J
Clinical Division, College of Pharmacy, University of Texas, Austin 78712.
Pharmacotherapy. 1991;11(4):296-302.
The objective of this study was to describe the postinduction clearance of carbamazepine (CBZ) in adult psychiatric patients by population pharmacokinetic analysis using the NONMEM program. Specifically, an estimate of CBZ clearance and insight into the effect of common patient characteristics on clearance were sought. Steady-state trough CBZ serum concentrations, CBZ dosing history, concomitant drug administration, and other data from 45 patients were collected retrospectively. A one-compartment model with first-order absorption and first-order elimination was used, with absorption rate, bioavailability, and volume of distribution fixed to literature values. No evidence was found that race, sex, age, ethanol use, smoking, and concomitant lithium significantly affected CBZ clearance. In the final model, clearance was based on lean body weight. The coefficient of variation for clearance estimates was 16.5%. Residual variability was modest. Estimates for volume of distribution, rates of absorption and elimination, and bioavailability could not be pursued rigorously. Although these results may assist in understanding CBZ disposition in this population, their general clinical application should be approached with caution.
本研究的目的是使用NONMEM程序通过群体药代动力学分析描述成年精神病患者中卡马西平(CBZ)诱导后的清除情况。具体而言,旨在估算CBZ清除率,并深入了解常见患者特征对清除率的影响。回顾性收集了45例患者的稳态谷CBZ血清浓度、CBZ给药史、合并用药情况及其他数据。采用具有一级吸收和一级消除的单室模型,将吸收速率、生物利用度和分布容积固定为文献值。未发现种族、性别、年龄、饮酒、吸烟和合并使用锂对CBZ清除率有显著影响。在最终模型中,清除率基于瘦体重。清除率估计值的变异系数为16.5%。残差变异性较小。分布容积、吸收和消除速率以及生物利用度的估计无法严格进行。尽管这些结果可能有助于理解该人群中CBZ的处置情况,但在临床中的普遍应用应谨慎对待。