Zherdev V P, Caccia S, Garattini S, Ekonomov A L
Eur J Drug Metab Pharmacokinet. 1982;7(3):191-6. doi: 10.1007/BF03189565.
The kinetic profiles of phenazepam and its hydroxylated derivative were compared in rat, dog, cat and man after administration of single oral doses of the parent compound. The absorption of phenazepam was reasonably rapid in all the species studied. Blood peak concentrations (Cmax) were reached at 1 h in rats (0.32 +/- 0.03 microgram/ml), at 0.5 h in dogs 0.54 +/- 0.10 microgram/ml), at about 2 h in cats (1.65 +/- 0.23 microgram/ml), about only at 4 h in man (0.038 microgram/ml) at the highest dose tested. The largest normalized (value/dose) Cmax and area under the curve (AUC) were observed in man, while the rat gave the lowest values. The half-life of phenazepam was about 60 h in man, 13.72 +/- 2.09 h in the cat, 6.35 +/- 2.32 h in the dog and 7.49 +/- 1.88 h in the rat (beta-half-life). 3-OH-phenazepam was rapidly detected in cat, rat, and dog blood but no measurable amounts (less than 3 ng/ml) were found in human blood. At the oral doses tested, the ratio of the AUC for 3-OH-phenazepam to phenazepam was 0.01, 0.48, and 0.53 in the dog, rat, and cat, respectively. The half-life of the metabolite was shorter than that of the parent compound in the dog, but it was comparable in the rat and longer in the cat. The results suggest that 3-OH-phenazepam might contribute to the overall pharmacological effects of the parent compound in those species in which it accumulates in significant amounts.
单次口服苯氮卓母体化合物后，在大鼠、狗、猫和人体内比较了苯氮卓及其羟基化衍生物的动力学特征。在所有研究的物种中，苯氮卓的吸收相当迅速。大鼠在1小时时达到血药峰浓度（Cmax）（0.32±0.03微克/毫升），狗在0.5小时时达到（0.54±0.10微克/毫升），猫在约2小时时达到（1.65±0.23微克/毫升），在最高测试剂量下，人仅在4小时时达到（0.038微克/毫升）。最大标准化（值/剂量）Cmax和曲线下面积（AUC）在人体内观察到最大，而大鼠的值最低。苯氮卓在人体内的半衰期约为60小时，猫为13.72±2.09小时，狗为6.35±2.32小时，大鼠为7.49±1.88小时（β半衰期）。在猫、大鼠和狗的血液中迅速检测到3-羟基苯氮卓，但在人血中未发现可测量的量（小于3纳克/毫升）。在所测试的口服剂量下，狗、大鼠和猫体内3-羟基苯氮卓与苯氮卓的AUC比值分别为0.01、0.48和0.53。该代谢物在狗体内的半衰期比母体化合物短，但在大鼠体内相当，在猫体内更长。结果表明，在3-羟基苯氮卓大量蓄积的物种中，它可能对母体化合物的整体药理作用有贡献。
