The Effect of Isradipine on Theophylline Pharmacokinetics in Healthy Volunteers

The effects of isradipine 2.5 mg and 5 mg on the disposition of theophylline were investigated in a placebo‐controlled, randomized, three‐way, crossover trial. Eleven healthy, nonsmoking men each received a treatment of placebo, and isradipine 2.5 mg and 5 mg every 12 hours for 6 consecutive days. On the morning of day 6, 2 hours after the isradipine dose, theophylline (solution) 5.0 mg/kg was administered orally, and blood samples were collected over 24 hours. A 2‐week washout period separated treatment sequences. Plasma samples were analyzed for theophylline using high‐performance liquid chromatography. Using a two‐way analysis of variance, no significant changes in apparent theophylline clearance were observed between placebo, and isradipine 2.5 and 5 mg (0.815 ± 0.164, 0.870 ± 0.212, and 0.827 ± 0.164 ml/min/kg, respectively; p=0.136). Similarly, no significant change in volume of distribution was noted. These findings suggest that isradipine at recommended dosages does not impair theophylline metabolism. 1993 Pharmacotherapy Publications Inc.