Herman R J, Van Pham J D, Szakacs C B
Department of Medicine, University of Saskatchewan, Saskatoon, Canada.
Clin Pharmacol Ther. 1989 Jul;46(1):18-25. doi: 10.1038/clpt.1989.101.
The effects of neomycin and cholestyramine on the disposition of lorazepam was examined in seven healthy drug-free men. Half-life as determined for the oral route was, in all subjects, 15% to 35% less than that determined for the intravenous route. Free oral clearance was slightly but not significantly less than free systemic clearance, but the ratio of the AUC of lorazepam glucuronide corrected for dose was twofold greater by the oral route. Urinary recoveries also differed (71.6% and 50.4%, oral versus intravenous). Neomycin and cholestyramine treatment resulted in a 19% to 26% reduction in half-life attendant on a 34% increase in free oral clearance and a 24% increase in free systemic clearance. This suggests that lorazepam undergoes significant enterohepatic recirculation in human beings and that there exists an extrahepatic pathway, at least for the intravenous route. Since pharmacokinetic measurements do not take these physiologic processes into account, the drug cannot properly be used as a marker of conjugative metabolism.
在7名未服用过药物的健康男性中研究了新霉素和消胆胺对劳拉西泮处置的影响。所有受试者口服途径的半衰期比静脉途径测定的半衰期短15%至35%。游离口服清除率略低于游离全身清除率，但差异不显著，而口服途径校正剂量后的劳拉西泮葡萄糖醛酸苷的AUC比值高两倍。尿回收率也有所不同（口服与静脉注射分别为71.6%和50.4%）。新霉素和消胆胺治疗使半衰期降低19%至26%，同时游离口服清除率增加34%，游离全身清除率增加24%。这表明劳拉西泮在人体内经历显著的肠肝循环，并且至少对于静脉途径存在肝外途径。由于药代动力学测量未考虑这些生理过程，因此该药物不能恰当地用作结合代谢的标志物。
