el Desoky E, Meinshausen J, Bühl K, Engel G, Harings-Kaim A, Drewelow B, Klotz U
Dr. Margarete Fischer-Bosch-Institut für Klinische Pharmakologie, Stuttgart, Germany.
Ther Drug Monit. 1993 Aug;15(4):281-8. doi: 10.1097/00007691-199308000-00004.
In three groups (each n = 12) of unselected hospitalized patients treated either with digoxin, theophylline, or gentamicin routinely performed TDM measurement of trough steady-state plasma levels (+ peak levels in case of gentamicin) was combined with a pharmacokinetic study at steady state (multiple blood sampling during one dosing interval). Pharmacokinetic parameters (apparent volume of distribution Vd, total plasma clearance CL) needed for individualization of dosage were evaluated by the Bayesian approach and a model-(in)dependent pharmacokinetic program (TOPFIT). Comparison of both methods revealed some small differences in the pharmacokinetic parameters for all three drugs. Mean deviations of the Bayesian estimates from the pharmacokinetic calculations of the three drugs ranged between 20 and 38% for Vd and between 13 and 22% for CL, indicating that the Bayesian approach provided reliable pharmacokinetic estimates for individualizing drug dosage under routine conditions. Therefore, it is suggested that routine TDM combined with Bayesian-based analyses can be regarded as an alternative to pharmacokinetic studies in clinically relevant populations.
在三组（每组n = 12）未经过挑选的住院患者中，分别接受地高辛、茶碱或庆大霉素治疗，常规进行谷浓度稳态血浆水平的治疗药物监测（对于庆大霉素还包括峰浓度），并结合稳态时的药代动力学研究（在一个给药间隔内进行多次血样采集）。通过贝叶斯方法和一个模型依赖（或非依赖）的药代动力学程序（TOPFIT）评估了剂量个体化所需的药代动力学参数（表观分布容积Vd、总血浆清除率CL）。两种方法的比较显示，三种药物的药代动力学参数存在一些小的差异。三种药物的贝叶斯估计值与药代动力学计算值的平均偏差，Vd在20%至38%之间，CL在13%至22%之间，这表明贝叶斯方法在常规条件下为药物剂量个体化提供了可靠的药代动力学估计。因此，建议常规治疗药物监测结合基于贝叶斯的分析可被视为临床相关人群中药代动力学研究的一种替代方法。
