Karhu David, El-Jammal Ali, Dupain Thibaut, Gaulin Delphine, Bouchard Sylvie
Labopharm Inc., Laval, QC, Canada.
Biopharm Drug Dispos. 2007 Sep;28(6):323-30. doi: 10.1002/bdd.561.
A three-way crossover study in 27 human volunteers was conducted to characterize the pharmacokinetics and to assess the dose proportionality of 100 mg, 200 mg and 300 mg strengths of a novel once-a-day tramadol controlled-release tablet (Tramadol Contramid OAD) following single-dose administration. Serial blood samples were collected at predefined timepoints over a 48 h period and racemic tramadol and O-desmethyltramadol concentrations in plasma were determined using a validated LC-MS/MS method. Pharmacokinetic parameters were derived using noncompartmental methods. Following dose normalization and logarithmic transformation of concentration-dependent parameters, the results were compared using analysis of variance (ANOVA). The residual variability thereby obtained was used to construct 90% classical confidence intervals. The two one-sided tests procedure was used for all pairwise comparisons. Dose proportionality was concluded since the 90% CI for the ratio of geometric means was included in the acceptance range of 0.80-1.25 for all comparisons.
在27名人类志愿者中进行了一项三交叉研究，以表征一种新型每日一次曲马多控释片（曲马多控释片OAD）100毫克、200毫克和300毫克规格单剂量给药后的药代动力学特征并评估剂量比例性。在48小时内的预定时间点采集系列血样，使用经过验证的液相色谱-串联质谱法（LC-MS/MS）测定血浆中消旋曲马多和O-去甲基曲马多的浓度。使用非房室方法推导药代动力学参数。在对浓度依赖性参数进行剂量归一化和对数转换后，使用方差分析（ANOVA）比较结果。由此获得的残余变异性用于构建90%的经典置信区间。所有成对比较均采用双向单侧检验程序。由于所有比较中几何均值比的90%置信区间均包含在0.80-1.25的接受范围内，因此得出剂量比例性结论。
