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.
Perreault
M M
MM
Groupe de Pharmacologie et Pharmacie Clinique, Hôtel-Dieu de Montréal, Canada.
Kazierad
D J
DJ
Wilton
J H
JH
Izzo
J L
JL
D000328:Adult; D002851:Chromatography, High Pressure Liquid; D004334:Drug Administration Schedule; D006801:Humans; D017275:Isradipine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008657:Metabolic Clearance Rate; D016037:Single-Blind Method; D013806:Theophylline / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D013806:Theophylline; D017275:Isradipine