Clifton G D, Blouin R A, Dilea C, Schran H F, Hassell A E, Gonasun L M, Foster T S
Drug Product Evaluation Unit, College of Pharmacy, University of Kentucky, Lexington 40536-0082.
J Clin Pharmacol. 1988 Jan;28(1):36-42. doi: 10.1002/j.1552-4604.1988.tb03098.x.
The pharmacokinetics and relative bioavailability of oral isradipine, a dihydropyridine calcium channel blocking agent, were determined in 42 normal male volunteers participating in two separate studies. Eighteen of the subjects received 2.5-, 5-, and 10-mg oral doses of isradipine solution (Study 1). The remaining 24 subjects received four 2.5-mg capsules, one 10-mg capsule, and 10 mg of isradipine as an oral solution (Study 2). Venous blood samples were obtained prior to and at frequent intervals after administration of each dose form. Plasma isradipine concentrations were measured by radioimmunoassay. No significant dose effect occurred with respect to any pharmacokinetic parameter except AUC and Cmax in Study 1. In Study 2, Cmax, tmax, and MRT were significantly different after the solution compared with the capsular formulations. The respective pharmacokinetic parameters (mean +/- SD) for the 10-mg solution and 10-mg capsule in Study 2 were time to maximum concentration, 0.40 +/- .28 and 1.57 +/- 0.44 hours; oral clearance, 284.9 +/- 105.3 and 317.0 +/- 138.4 L/hr; elimination half-life, 5.36 +/- 1.8 and 6.63 +/- 2.4 hrs, respectively. Headache, dizziness, and tachycardia were the most frequent adverse effects in both studies.
在两项独立研究中，对42名正常男性志愿者测定了二氢吡啶类钙通道阻滞剂口服异搏定的药代动力学及相对生物利用度。18名受试者接受了2.5毫克、5毫克和10毫克口服异搏定溶液（研究1）。其余24名受试者接受了四粒2.5毫克胶囊、一粒10毫克胶囊以及10毫克异搏定口服溶液（研究2）。在给予每种剂型之前及之后的多个时间点采集静脉血样。采用放射免疫分析法测定血浆异搏定浓度。在研究1中，除AUC和Cmax外，未观察到任何药代动力学参数有显著剂量效应。在研究2中，溶液剂型后的Cmax、tmax和MRT与胶囊剂型相比有显著差异。研究2中10毫克溶液和10毫克胶囊各自的药代动力学参数（平均值±标准差）为：达峰时间，分别为0.40±0.28和1.57±0.44小时；口服清除率，分别为284.9±105.3和317.0±138.4升/小时；消除半衰期，分别为5.36±1.8和6.63±2.4小时。头痛、头晕和心动过速是两项研究中最常见的不良反应。
