Effects of cimetidine and ranitidine on the pharmacokinetics of a chronotherapeutically formulated once-daily theophylline preparation (Uniphyl).
The effects of cimetidine and ranitidine on the steady-state pharmacokinetics, safety, and efficacy of a chronotherapeutically formulated (CTF), once-daily theophylline preparation (Uniphyl) were evaluated in 12 adult patients with asthma. In this randomized, double-blind, three-way crossover study, patients received a fixed dose of CTF-theophylline and concurrent cimetidine, ranitidine, or placebo for a period of 7 days each. Asthma symptoms, drug side effects, and beta 2-agonist inhaler use were recorded daily. Venous blood sampling for pharmacokinetic assessment was done over a complete dosing interval on day 7 of each phase. Coadministration of cimetidine, but not ranitidine, was associated with a significant decrease in the apparent oral clearance of theophylline (2.47 +/- 0.91 vs 1.85 +/- 0.63 L/hr; P = 0.004) and increases in the theophylline area under the curve (233.48 +/- 58.99 vs 307.43 +/- 79.07 mg/L/hr; P = 0.003), peak concentration (13.2 +/- 2.8 vs 16.7 +/- 3.7 mg/L; P = 0.002), and trough concentration (6.4 +/- 2.5 vs 9.0 +/- 3.0 mg/L; P = 0.008). Despite the changes in theophylline pharmacokinetic parameters during cimetidine treatment, no significant differences in asthma symptom scores or side effects were seen when once-daily CTF-theophylline was administered concomitantly with cimetidine, ranitidine, or placebo.
Department of Medicine, Toronto East General Hospital, Ontario, Canada.
I M
IM
Fraser
K M
KM
Buttoo
S E
SE
Walker
J H
JH
Stewart
N
N
Babul
D000328:Adult; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology; D002927:Cimetidine / Q000009:adverse effects / Q000494:pharmacology*; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011899:Ranitidine / Q000009:adverse effects / Q000494:pharmacology*; D013806:Theophylline / Q000008:administration & dosage / Q000493:pharmacokinetics*
D003692:Delayed-Action Preparations; D002927:Cimetidine; D011899:Ranitidine; D013806:Theophylline