Razak T A, McNeil J J, Sewell R B, Drummer O H, Smallwood R A, Conway E L, Louis W J
University of Melbourne, Clinical Pharmacology and Therapeutics Unit, Heidelberg, Victoria, Australia.
Clin Pharmacol Ther. 1990 Apr;47(4):463-9. doi: 10.1038/clpt.1990.58.
The present study was designed to compare the pharmacokinetic handling of a single oral dose of nicardipine in normal subjects and in patients with hepatic cirrhosis and to compare the sensitivity of the two groups to its hypotensive effect. Nicardipine plasma concentrations were substantially higher in the subjects with hepatic cirrhosis with impaired antipyrine clearance, as shown by a significantly higher average Cmax and AUC. The terminal elimination half-life in this group varied from 0.8 to 60.2 hours (median, 11.7 hours), compared with 0.6 to 4.1 hours (median, 1.4 hours) in the group of eight subjects with normal liver function. In the cirrhotic patients with impaired antipyrine clearance, the AUC of the pyridine metabolite averaged 10% of that of the parent drug, whereas in normal subjects the ratio averaged 48%. This finding suggests less conversion of nicardipine to this metabolite in subjects with impaired hepatic function. Peak blood pressure decreases were greater in the cirrhotic group, which was in keeping with the higher plasma levels in these subjects.
本研究旨在比较正常受试者和肝硬化患者单次口服硝苯地平后的药代动力学过程，并比较两组对其降压作用的敏感性。肝硬化患者的安替比林清除率受损，硝苯地平血浆浓度显著更高，表现为平均Cmax和AUC显著更高。该组的终末消除半衰期为0.8至60.2小时（中位数为11.7小时），而肝功能正常的8名受试者组为0.6至4.1小时（中位数为1.4小时）。在安替比林清除率受损的肝硬化患者中，吡啶代谢物的AUC平均为母体药物的10%，而在正常受试者中该比例平均为48%。这一发现表明肝功能受损的受试者中硝苯地平向该代谢物的转化较少。肝硬化组的血压峰值下降更大，这与这些受试者较高的血浆水平一致。
