Horton T L, Pollack G M
Division of Pharmaceutics, School of Pharmacy, University of North Carolina, Chapel Hill 27599-7360.
J Pharm Sci. 1991 Dec;80(12):1147-52. doi: 10.1002/jps.2600801211.
Morphine (2.5 mg/kg) was administered iv to intact (I), bile duct-cannulated (BC), and bile duct-cannulated--renal-ligated (BC-RL) rats (n = 4 per group) to investigate the extent of enterohepatic recirculation and renal metabolism of the drug. A decrease in the serum area under the concentration-time curve (AUC) was observed for the BC in comparison with I rats. From these AUC values, it was determined that approximately 16% of the administered dose was subject to enterohepatic recirculation. In addition, a statistically significant (p less than 0.05) decrease in the systemic clearance of morphine was observed in the BC-RL rats compared with the BC animals (55.2 +/- 17.2 versus 31.4 +/- 8.5 mL/min/kg). This decrement in systemic clearance appeared to be the result of a significant decrease in the formation clearance of morphine glucuronide after ligation of the renal pedicles (23.2 +/- 4.8 versus 10.9 +/- 5.0 mL/min/kg). Renal metabolic clearance was calculated as 15.7 mL/min/kg, accounting for 28.5% of the systemic clearance of morphine. Hepatic clearance (31.4 +/- 8.5 mL/min/kg) accounted for 56.8% of total systemic clearance.
给完整的（I）、胆管插管的（BC）和胆管插管且肾结扎的（BC-RL）大鼠（每组n = 4）静脉注射吗啡（2.5 mg/kg），以研究该药物的肠肝循环程度和肾脏代谢情况。与I组大鼠相比，观察到BC组大鼠血清浓度-时间曲线下面积（AUC）降低。根据这些AUC值，确定给药剂量中约16%经历了肠肝循环。此外，与BC组动物相比，BC-RL组大鼠吗啡的全身清除率出现统计学显著降低（p < 0.05）（55.2 ± 17.2对31.4 ± 8.5 mL/min/kg）。全身清除率的这种降低似乎是肾蒂结扎后吗啡葡糖醛酸苷生成清除率显著降低的结果（23.2 ± 4.8对10.9 ± 5.0 mL/min/kg）。肾脏代谢清除率计算为15.7 mL/min/kg，占吗啡全身清除率的28.5%。肝脏清除率（31.4 ± 8.5 mL/min/kg）占全身总清除率的56.8%。
