Rameis H, Hitzenberger G, Kutscher R, Manigley C
Wiener Arbeitsgruppe für angewandte klinische Pharmakologie und Therapie, Wien, Austria.
Int J Clin Pharmacol Ther. 1994 Sep;32(9):458-65.
The basis of this investigation was a trial on the relative bioavailability of a recently developed galenic formulation of piracetam. The open, randomized, single-blind crossover study was performed in 16 healthy male volunteers aged between 20 and 31 years. Under fasting conditions, they were given a single oral dose of 1600 mg piracetam either of the test drug or the reference drug. Blood samples and urine specimens were collected over 24 hours. The quantitative analysis was performed with a high sensitive HPLC-method. The pharmacokinetic analysis was carried out with the PC-based program TopFit. An identical bioavailability of the test drug was found (AUC0-24, AUC0-infinity, Cmax, by comparison to the reference drug. No relevant difference in piracetam excretion between test and reference drug was found, however, in contrast to previous references only about two thirds of the given oral dose could be detected in the urine after administration. A statistically significant difference (p = 0.001) between total clearance and renal clearance was observed. Because an incomplete absorption of the drug in the upper gastrointestinal tract is excluded, an additional extrarenal pathway of piracetam must be discussed; the hypothesis of an exclusive renal elimination of this drug should be overruled.
本研究的基础是一项关于最近开发的吡拉西坦盖仑制剂相对生物利用度的试验。该开放、随机、单盲交叉研究在16名年龄在20至31岁之间的健康男性志愿者中进行。在禁食条件下，他们单次口服1600毫克试验药物或参比药物中的吡拉西坦。在24小时内采集血样和尿样。采用高灵敏度HPLC法进行定量分析。使用基于PC的TopFit程序进行药代动力学分析。与参比药物相比，发现试验药物具有相同的生物利用度（AUC0-24、AUC0-∞、Cmax）。然而，试验药物和参比药物之间在吡拉西坦排泄方面未发现相关差异，不过，与之前的参考文献相比，给药后尿中仅能检测到约三分之二的口服剂量。观察到总清除率和肾清除率之间存在统计学显著差异（p = 0.001）。由于排除了药物在上消化道的不完全吸收，必须讨论吡拉西坦的另一种肾外途径；该药物仅通过肾脏消除的假设应被推翻。
