Shaw-Stiffel T A, Walker S E, Ogilvie R I, Leenen F H
Yale University-Affiliated G.I. Program, Bridgeport Hospital, CT 06610.
Clin Pharmacol Ther. 1994 Jun;55(6):661-9. doi: 10.1038/clpt.1994.83.
The pharmacokinetic and pharmacodynamic interactions after 7 days of oral treatment with nisoldipine (10 mg twice daily) and propranolol (80 mg twice daily) were investigated in a partially randomized, placebo-controlled crossover study of 12 healthy volunteers.
At the end of each treatment period, pharmacokinetic parameters were measured, along with blood pressure, heart rate, cardiac function, systemic hemodynamics, plasma catecholamines, forearm blood flow, and apparent hepatic blood flow (estimated by the clearance of indocyanine green dye).
After 7 days of treatment with nisoldipine and propranolol, neither drug altered the other's bioavailability or elimination parameters, and propranolol did not change the area under the plasma concentration-time curve of nisoldipine's metabolite, N-9425. Nisoldipine alone increased apparent hepatic blood flow and forearm blood flow compared with the other treatment groups but, with the addition of propranolol, both of these parameters were similar to those in the placebo group. Changes in the other hemodynamic parameters were consistent with the known effects of these drugs, and no differences in plasma catecholamine levels were detected.
In contrast to the findings with single-dose treatment, administration of the combination of nisoldipine and propranolol for 7 days is not associated with any measurable kinetic interactions, although significant hemodynamic interactions do occur.
在一项针对12名健康志愿者的部分随机、安慰剂对照交叉研究中，研究了硝苯地平（每日两次，每次10毫克）和普萘洛尔（每日两次，每次80毫克）口服治疗7天后的药代动力学和药效学相互作用。
在每个治疗期结束时，测量药代动力学参数，同时测量血压、心率、心功能、全身血流动力学、血浆儿茶酚胺、前臂血流量和表观肝血流量（通过吲哚菁绿染料清除率估算）。
硝苯地平和普萘洛尔治疗7天后，两种药物均未改变对方的生物利用度或消除参数，普萘洛尔也未改变硝苯地平代谢物N-9425的血浆浓度-时间曲线下面积。与其他治疗组相比，单独使用硝苯地平可增加表观肝血流量和前臂血流量，但加入普萘洛尔后，这两个参数均与安慰剂组相似。其他血流动力学参数的变化与这些药物的已知作用一致，未检测到血浆儿茶酚胺水平的差异。
与单剂量治疗的结果相反，硝苯地平和普萘洛尔联合使用7天与任何可测量的动力学相互作用无关，尽管确实发生了显著的血流动力学相互作用。
