Launay M C, Milano G, Iliadis A, Frenay M, Namer N
Laboratoire de Pharmacocinétique, INSERM U 278, Faculté de Pharmacie, Marseille, France.
Br J Cancer. 1989 Jul;60(1):89-92. doi: 10.1038/bjc.1989.226.
The aim of this study was to find a procedure allowing estimation of individual pharmacokinetic parameters for adriamycin with minimal cost and disturbance for the patient. Twenty-five patients with breast cancer were treated by short infusion of adriamycin at a dose of 12 mg m-2 week-1 (41 courses). Population characteristics were determined on 15 randomly chosen courses (10 patients, group I) in order to define two optimal sampling times (26 min and 24 h) and to perform Bayesian estimation on the remaining 26 courses (17 patients, group II). For patients of group II, Bayesian estimation (BE) associated with a reduced sub-optimal sampling protocol (20 min and 24 h) was compared with maximum likelihood estimation (MLE), the classical procedure. Regression analysis of clearance values obtained after BE versus MLE indicated a high correlation coefficient (r = 0.969) with the slope (a = 0.991 +/- 0.085) and the intercept (b = 2.271 +/- 4.810) close to 1 and 0 respectively. This original method is thus valid to measure accurately adriamycin clearance; it improves patient comfort and can be used routinely.
本研究的目的是找到一种方法，以最小的成本和对患者的干扰来估算阿霉素的个体药代动力学参数。25例乳腺癌患者接受阿霉素短时间输注治疗，剂量为12 mg m-2 周-1（共41个疗程）。为了确定两个最佳采样时间（26分钟和24小时）并对其余26个疗程（17例患者，第二组）进行贝叶斯估计，在15个随机选择的疗程（10例患者，第一组）中确定总体特征。对于第二组患者，将与简化的次优采样方案（20分钟和24小时）相关的贝叶斯估计（BE）与经典方法最大似然估计（MLE）进行比较。对BE与MLE后获得的清除率值进行回归分析，结果显示相关系数较高（r = 0.969），斜率（a = 0.991 +/- 0.085）和截距（b = 2.271 +/- 4.810）分别接近1和0。因此，这种原始方法可有效地准确测量阿霉素清除率；它提高了患者的舒适度，可常规使用。
