Effect of moricizine on the pharmacokinetics of single-dose theophylline in healthy subjects.
We studied the effect of multiple oral doses of moricizine on the pharmacokinetics of theophylline in healthy male subjects. Twelve subjects initially received two single oral doses of theophylline, one in the form of immediate-release Aminophyllin on day 1 and the other in the form of controlled-release Theo-Dur on day 3. Multiple oral doses of moricizine (Ethmozine, 250 mg every 8 h) began on day 5 and continued for 18 days. While receiving moricizine, the subjects were again given the two formulations of theophylline in the same order on days 19 and 21. Theophylline pharmacokinetic profiles were obtained over 36 h after all theophylline administrations. Multiple-dose moricizine administration significantly decreased (p < 0.0005) theophylline area under the curve by 32 and 36% after Aminophyllin and Theo-Dur, respectively. Theophylline t1/2 was also significantly decreased (p < 0.02) by concomitant moricizine dosing. Moricizine had no apparent effect on theophylline absorption after Aminophyllin, based on the lack of changes in the maximum plasma concentration (Cmax) and the time to reach Cmax; however, moricizine administration did decrease (p < 0.0005) the Cmax of theophylline after Theo-Dur. We conclude that these pharmacokinetic changes are most likely due to enzyme induction mediated by moricizine. Consequently, concomitant use of moricizine and theophylline may necessitate the administration of more frequent and higher doses of theophylline.
Pieniaszek
H J
HJ
Drug Metabolism and Pharmacokinetics Section, Du Pont Merck Pharmaceutical Company, Newark, Delaware 19714.
Davidson
A F
AF
Benedek
I H
IH
D000284:Administration, Oral; D000328:Adult; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004347:Drug Interactions; D006801:Humans; D008297:Male; D016293:Moricizine / Q000494:pharmacology*; D013806:Theophylline / Q000493:pharmacokinetics*
D003692:Delayed-Action Preparations; D016293:Moricizine; D013806:Theophylline