Gender differences in hepatic induction and inhibition of theophylline pharmacokinetics and metabolism.
This investigation examined whether or not a gender-related effect on theophylline pharmacokinetics and metabolism exists in smoking and nonsmoking subjects with and without the concurrent administration of cimetidine. With a crossover design, 28 healthy men and premenopausal women (14 in each group) were administered intravenous aminophylline before (phase 1) and during (phase 2) a 10-day course of cimetidine, 300 mg four times a day. Statistically significant gender- and smoking-related effects were seen for theophylline half-life and clearance in phase 1, but only the smoking effect was statistically significant for these pharmacokinetic parameters in phase 2. Urinary metabolite excretion patterns demonstrated a greater percentage of excretion of 3-methylxanthine in female smokers than in male smokers in phase 1. Time-averaged urinary clearance of 1,3-dimethyluric acid was greater in female smokers than in male smokers. In phase 2, a significant reduction in the clearance of 1,3-dimethyluric acid was noted in female smokers but not in any other group. The results of our investigation suggest that a significant difference in the pharmacokinetics of theophylline exists that is related to gender and smoking status. Theophylline metabolism also seems to vary according to these factors. Administration of cimetidine results in a significant reduction in clearance of theophylline and abolishes the gender differences but not the smoking differences.
Jennings
T S
TS
Department of Pharmacy Services, Mary Imogene Bassett Hospital, Cooperstown, New York 13326-1394.
Nafziger
A N
AN
Davidson
L
L
Bertino
J S
JS
D000328:Adult; D000704:Analysis of Variance; D002927:Cimetidine / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D006207:Half-Life; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000378:metabolism; D012727:Sex Characteristics; D012907:Smoking / Q000378:metabolism*; D013806:Theophylline / Q000378:metabolism* / Q000493:pharmacokinetics
D002927:Cimetidine; D013806:Theophylline; D006899:Mixed Function Oxygenases