Witkamp R F, Kolker H J, Nijmeijer S M, Noordhoek J, van Miert A S
Department of Veterinary Basic Sciences, University of Utrecht, The Netherlands.
Res Vet Sci. 1993 Jul;55(1):31-7. doi: 10.1016/0034-5288(93)90030-j.
Effects of recombinant bovine somatotrophin (rBST) on in vivo and in vitro oxidative drug metabolism were studied in male rats. rBST was given subcutaneously at a dose of 250 or 500 micrograms 100 g-1 bodyweight 24 h-1 in different dosage patterns. Sulphadimidine (SDD) plasma clearance, urinary excretion of 6-hydroxy-SDD and the in vitro microsomal SDD-hydroxylations were only inhibited when rBST was given in three injections per 24 hours. The hepatic microsomal ethylmorphine N-demethylation rate and the testosterone hydroxylation rate at the 6 beta position were significantly reduced after one rBST injection per 24 hours. Microsomal testosterone hydroxylation rates at the 16 alpha and 2 alpha-positions were reduced depending on the frequency of rBST administration. It is concluded that the inhibition of in vivo and in vitro drug oxidation in rats by rBST is associated with selective changes in activity of cytochrome P450 enzymes in the liver.
研究了重组牛生长激素（rBST）对雄性大鼠体内和体外氧化药物代谢的影响。以不同给药模式，按250或500微克/100克体重的剂量皮下注射rBST，每24小时一次。仅当每24小时注射三次rBST时，磺胺二甲嘧啶（SDD）的血浆清除率、6-羟基-SDD的尿排泄量以及体外微粒体SDD-羟基化反应才受到抑制。每24小时注射一次rBST后，肝微粒体N-脱甲基乙基吗啡速率以及6β位睾酮羟化速率显著降低。16α和2α位微粒体睾酮羟化速率的降低取决于rBST的给药频率。得出的结论是，rBST对大鼠体内和体外药物氧化的抑制作用与肝脏中细胞色素P450酶活性的选择性变化有关。
