Putri Ratih S I, Setiawati Effi, Aziswan Syifa A, Ong Fenny, Tjandrawinata Raymond R, Susanto Liana W
PT Equilab International Bioavailability and Bioequivalence Laboratory, Jl. RS Fatmawati Persil 33, 12430 Jakarta, Indonesia.
Dexa Laboratories of Biomolecular Sciences (DLBS), Industri Selatan V Block PP No. 7, Jababeka Industrial Estate II, Cikarang, 17550 West Java, Indonesia.
Sci Pharm. 2016 Nov 18;84(4):715-723. doi: 10.3390/scipharm84040715.
The present study aimed to compare pharmacokinetic parameters of two pramipexole 0.25 mg formulations in order to show bioequivalence. The study was conducted in a randomized, open-label, two-period, two-sequence, and crossover design, involving 23 healthy volunteers. One of the 0.25 mg formulations of pramipexole evaluated in the study was manufactured by PT Dexa Medica, Palembang, Indonesia, the other, used as the reference, by Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, Germany. All eligible subjects were required to fast before each drug administration period, which was separated by a one-week washout period. Pramipexole concentrations in plasma were assayed using a validated ultra performance liquid chromatography with mass spectrometry (UPLC-MS/MS) detector. The evaluated pharmacokinetic parameters included the area under the plasma concentration curve from time zero to the last observed measurable concentration (AUC), the area under the plasma concentration curve extrapolated to infinite time (AUC), the maximum plasma concentration (C), the time to reach C (t), and the plasma concentration half-life (t). To evaluate the bioequivalence of those two pramipexole formulations, 90% confidence intervals (CIs) for geometric mean ratios of both formulations were calculated for AUC and C parameters, while t and t differences were analyzed on the non-transformed data using Wilcoxon matched-pairs and a Student's paired -test, respectively. The 90% CIs for the geometric mean ratios of the two pramipexole formulations were 95.89% (90.73%-101.34%), 95.53% (89.75%-101.68%), and 92.11% (84.35%-100.58%) for AUC, AUC, and C, respectively. There were no statistically significant differences for t and t between the two pramipexole formulations. It is concluded that two pramipexole formulations in this study were bioequivalent.
本研究旨在比较两种0.25毫克普拉克索制剂的药代动力学参数，以证明生物等效性。该研究采用随机、开放标签、两期、两序列和交叉设计，纳入了23名健康志愿者。本研究中评估的一种0.25毫克普拉克索制剂由印度尼西亚巨港的PT Dexa Medica公司生产，另一种用作参比制剂，由德国莱茵河畔英格尔海姆的勃林格殷格翰制药有限公司生产。所有符合条件的受试者在每个给药期前均需禁食，给药期之间间隔一周的洗脱期。采用经过验证的超高效液相色谱-质谱联用（UPLC-MS/MS）检测器测定血浆中的普拉克索浓度。评估的药代动力学参数包括从零时间到最后一次可观测到的可测量浓度的血浆浓度曲线下面积（AUC）、外推至无限时间的血浆浓度曲线下面积（AUC）、最大血浆浓度（C）、达到C的时间（t）以及血浆浓度半衰期（t）。为评估这两种普拉克索制剂的生物等效性，计算了两种制剂AUC和C参数几何平均比值的90%置信区间（CI），而t和t差异分别使用Wilcoxon配对检验和学生配对检验对未转换数据进行分析。两种普拉克索制剂几何平均比值的90%CI分别为：AUC为95.89%（90.73%-101.34%）、AUC为95.53%（89.75%-101.68%）、C为92.11%（84.35%-100.58%）。两种普拉克索制剂之间的t和t无统计学显著差异。结论为本研究中的两种普拉克索制剂具有生物等效性。
