Gut I, Becker B A
Arch Toxicol. 1975 Sep 5;34(1):61-70. doi: 10.1007/BF00353340.
Nature of considerable variability of hexobarbital sleeping time and drug metabolism efficiency within a single strain of rats were investigated. Wistar or Sprague-Dawley rats with shorter than average hexobarbital sleeping time had also higher rates of in vitro hepatic microsomal metabolism of hexobarbital, aminopyrine, aniline and benzene, higher liver weight, microsomal protein content and P-450 level, and faster hexobarbital blood level decline (but similar volumes of distribution) after intraperitoneal hexobarbital sodium than those with relatively longer hexobarbital sleeping time, but awakened with the same hexobarbital blood level. The differences were maintained throughout the life of rats and inherited in their offspring. It indicated a possible genetic control of hexobarbital sleeping time and efficiency of drug metabolisms with apparent differences in selection response for Type I and Type II substrates (hexobarbital and aminopyrine vs aniline): it might indicate different heredity mechanism for these types of substrates. Stronger hexobarbital narcotic effect in females was associated with the rate of hexobarbital metabolism, but also with higher brain sensitivity. Hexobarbital sleeping time pattern indicated more general pattern of drug metabolism (better for Type I substrates) and success of selection of rats for different efficiency of drug metabolism (up to 8-fold differences in F5 generation) suggested considerable genetic non-homogeneity of two common strains of laboratory rats.
研究了同一品系大鼠中己巴比妥睡眠时间和药物代谢效率存在显著变异性的本质。己巴比妥睡眠时间短于平均水平的Wistar或Sprague-Dawley大鼠，其体外肝微粒体对己巴比妥、氨基比林、苯胺和苯的代谢率也更高，肝脏重量、微粒体蛋白含量和P-450水平更高，腹腔注射己巴比妥钠后己巴比妥血药浓度下降更快（但分布容积相似），而己巴比妥睡眠时间相对较长但被相同己巴比妥血药浓度唤醒的大鼠则不然。这些差异在大鼠的整个生命过程中持续存在，并在其后代中遗传。这表明己巴比妥睡眠时间和药物代谢效率可能受遗传控制，对I型和II型底物（己巴比妥和氨基比林与苯胺）的选择反应存在明显差异：这可能表明这些类型底物的遗传机制不同。雌性大鼠中较强的己巴比妥麻醉作用与己巴比妥代谢率有关，但也与较高的脑敏感性有关。己巴比妥睡眠时间模式表明了更普遍的药物代谢模式（对I型底物更好），并且选择不同药物代谢效率的大鼠获得成功（F5代中差异高达8倍），这表明两种常见实验大鼠品系存在相当大的遗传非均一性。
