Back D J, Macnee C M, Orme M L, Rowe P H, Smith E
Biochem Pharmacol. 1984 May 15;33(10):1595-600. doi: 10.1016/0006-2952(84)90279-x.
Previous in vivo studies have suggested that phenobarbitone increases the first pass clearance of norethindrone in the rat by induction of enzymes both in the gut wall and liver. In the present study phenobarbitone caused an increase in both the production of highly polar ether-extractable metabolites and the conjugation of the steroid as it crossed the wall of the everted gut sac preparation. In addition, there was a marked increase in the uptake of norethindrone into the liver followed by increased phase I metabolism in the isolated perfused liver. As expected for a highly cleared drug, enzyme induction had no measurable effect on the terminal half-life of norethindrone in the perfused liver preparation.
先前的体内研究表明，苯巴比妥可通过诱导大鼠肠壁和肝脏中的酶来增加炔诺酮的首过清除率。在本研究中，苯巴比妥使高度极性的醚提取物代谢物的生成以及甾体在穿过外翻肠囊制剂肠壁时的结合作用均增加。此外，炔诺酮在肝脏中的摄取显著增加，随后在离体灌注肝脏中其I相代谢增加。正如对高清除率药物所预期的那样，酶诱导对灌注肝脏制剂中炔诺酮的末端半衰期没有可测量的影响。
