Fechner Jörg, Ihmsen Harald, Hatterscheid Dirk, Jeleazcov Christian, Schiessl Christine, Vornov James J, Schwilden Helmut, Schüttler Jürgen
Department of Anesthesiology, University of Erlangen-Nuremberg, Germany.
Anesthesiology. 2004 Sep;101(3):626-39. doi: 10.1097/00000542-200409000-00011.
GPI 15715 is a new water-soluble prodrug that is hydrolyzed to release propofol. The objectives of this crossover study in volunteers were to investigate the pharmacokinetics and pharmacodynamics of GPI 15715 in comparison with propofol emulsion.
In two separate sessions, nine healthy male volunteers (19-35 yr, 70-86 kg) received GPI 15715 and propofol emulsion as a target controlled infusion over 60 min. In the first 20 min, the propofol target concentration increased linearly to 5 microg/ml. Subsequently, the targets were reduced to 3 microg/ml and 1.5 microg/ml for 20 min each. The plasma concentrations of GPI 15715 and propofol were measured from arterial and venous blood samples up to 24 h and pharmacokinetics were analyzed. The pharmacodynamic effect was measured by the median frequency of the power spectrum of the electroencephalogram, and a sigmoid model with effect compartment was fitted to the data.
Compared with propofol emulsion, propofol from GPI 15715 showed a different disposition function and especially larger volumes of distribution. The propofol effect site concentration for half maximum effect was 2.0 +/- 0.5 microg/ml for GPI 15715 and 3.0 +/- 0.7 microg/ml for propofol emulsion (P < 0.05). Propofol from GPI 15715 did not show a hysteresis between plasma concentration and effect.
Compared with propofol emulsion, propofol from GPI 15715 showed different pharmacokinetics and pharmacodynamics, particularly a higher potency with respect to concentration. These differences may indicate an influence of the formulation.
GPI 15715是一种新型水溶性前体药物，可水解释放丙泊酚。本交叉研究在志愿者中的目的是比较GPI 15715与丙泊酚乳剂的药代动力学和药效学。
在两个独立的时段，9名健康男性志愿者（19 - 35岁，70 - 86千克）接受GPI 15715和丙泊酚乳剂作为目标控制输注，持续60分钟。在最初的20分钟内，丙泊酚目标浓度线性增加至5微克/毫升。随后，目标浓度分别降至3微克/毫升和1.5微克/毫升，各持续20分钟。采集动脉和静脉血样，测定长达24小时的GPI 15715和丙泊酚血浆浓度，并分析药代动力学。通过脑电图功率谱的中位频率测量药效学效应，并将具有效应室的S形模型拟合至数据。
与丙泊酚乳剂相比，GPI 15715中的丙泊酚表现出不同的处置功能，尤其是分布容积更大。GPI 15715达到半数最大效应时的丙泊酚效应室浓度为2.0±0.5微克/毫升，丙泊酚乳剂为3.0±0.7微克/毫升（P < 0.05）。GPI 15715中的丙泊酚在血浆浓度和效应之间未显示滞后现象。
与丙泊酚乳剂相比，GPI 15715中的丙泊酚表现出不同的药代动力学和药效学，尤其是在浓度方面具有更高的效能。这些差异可能表明制剂的影响。
