The Pharmacokinetics of Oral Isradipine in Normal Volunteers

Abstract

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 C_max in Study 1. In Study 2, C_max, t_max, 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.