Hanyok J J, Chow M S, Kluger J, Izard M W
Department of Pharmacy Services, Hartford Hospital, CT 06115.
J Clin Pharmacol. 1988 Sep;28(9):831-6. doi: 10.1002/j.1552-4604.1988.tb03224.x.
The pharmacokinetics and pharmacodynamics of verapamil were investigated in six chronic hemodialysis patients. A single oral 120-mg dose was administered both on a non-hemodialysis day and a hemodialysis day separated by greater than or equal to 7 days. Blood pressure and PR interval were measured simultaneously with each blood sample. Plasma verapamil and norverapamil concentrations were analyzed by high pressure liquid chromatography. The mean Cmax, tmax, AUC, apparent plasma clearance, and terminal t 1/2 were 190 +/- 108 ng/mL, 0.6 +/- 0.2 hour, 676 +/- 443 ng.hr/mL, 3926 +/- 1933 mL/min, and 11.4 +/- 4.0 hr, respectively, on the nonhemodialysis day. The dialysis clearance of verapamil and norverapamil was negligible. The t 1/2 during hemodialysis was 3.6 +/- 1.1 hr, compared with 3.4 +/- 0.7 hr during the same period of time postdose on the nonhemodialysis day (NS, P greater than .05). Systolic and diastolic blood pressure decreased for up to 4 hours postdose, whereas the PR interval tended to increase. Conclusions include: (1) the single oral-dose pharmacokinetics and pharmacodynamics of verapamil in chronic hemodialysis patients are similar to published data in normal subjects and cardiac patients and (2) verapamil and norverapamil are not significantly removed by hemodialysis, so that supplemental doses are not necessary.
在6名慢性血液透析患者中研究了维拉帕米的药代动力学和药效学。在非血液透析日和间隔大于或等于7天的血液透析日分别单次口服120mg剂量。每次采集血样时同时测量血压和PR间期。采用高压液相色谱法分析血浆维拉帕米和去甲维拉帕米浓度。在非血液透析日，平均Cmax、tmax、AUC、表观血浆清除率和终末t1/2分别为190±108ng/mL、0.6±0.2小时、676±443ng·hr/mL、3926±1933mL/min和11.4±4.0小时。维拉帕米和去甲维拉帕米的透析清除率可忽略不计。血液透析期间的t1/2为3.6±1.1小时，相比之下，非血液透析日给药后同一时间段的t1/2为3.4±0.7小时（无显著性差异，P＞0.05）。给药后收缩压和舒张压下降长达4小时，而PR间期有增加趋势。结论包括：（1）慢性血液透析患者中维拉帕米的单次口服剂量药代动力学和药效学与正常受试者和心脏病患者已发表的数据相似；（2）血液透析不会显著清除维拉帕米和去甲维拉帕米，因此无需补充剂量。
