Influence of Oral Contraceptive Use and Cigarette Smoking, Alone and Together, on Antipyrine Pharmacokinetics

Abstract

The pharmacokinetics of antipyrine following a single 1-g intravenous dose was determined in 63 healthy women. Subjects were divided into 4 groups as follows: 1) cigarette smokers using low-dose oral contraceptives (n = 15); 2) nonsmokers using low-dose oral contraceptives (n = 12); 3) cigarette smokers not using oral contraceptives (n = 10); and 4) controls, neither cigarette smokers nor oral contraceptive users. Plasma antipyrine concentrations during 24 to 48 hours after dosage were measured by high-performance liquid chromatography. Mean kinetic variables in the nonsmoking, non-oral contraceptive using control group were: volume of distribution, 37.7 L; elimination half-life, 13.2 hours; and clearance, 34.4 mL/min. In cigarette smoking, non-oral contraceptive users versus controls, elimination half-life was reduced (8.0 vs. 13.2 hours, P < 0.05) and clearance increased (56.0 vs. 34.4 mL/min, P < 0.05). In nonsmoker oral contraceptive users, the reverse was true (elimination half-life was significantly increased: 16.6 vs. 13.2 hours, P < 0.05; and clearance was significantly decreased: 24.8 vs. 34.4 mL/min, P < 0.05). In smokers who were using oral contraceptives, values were not significantly different from controls (elimination half-life, 11.2 hours; clearance, 39.5 mL/min). Volume of distribution did not differ among the four groups. Thus the opposing effects on antipyrine clearance of the induction of metabolism by cigarette smoking and the inhibition due to low dose oral contraceptive use in effect negate each other when combined in humans.

Plasma tacrine concentrations are significantly increased by concomitant hormone replacement therapy

“…Some earlier studies have reported inhibitory effects of oral contraceptive steroids on the clearance of caffeine, theophylline, and antipyrine (INN, phenazone)-all drugs metabolized by CYP1A2. [26][27][28][29] The results of this study with HRT that contained estradiol and levonorgestrel are therefore consistent with those obtained earlier with oral contraceptives. In vitro studies suggest that synthetic progestogens may have significant effects on oxidative drug metabolism in vivo and that there should be little difference in the inhibitory potential of different progestogens.…”

Exact profiles of 13CO2 recovery in breath air after per oral administration of [13C]methacetin in two groups of different ages

“…Likely candidates were gender, use of hormonal contraception, smoking status, and body constitution [29][30][31][32][33]. Even with definitely too small numbers of cigarette smokers, women on hormonal contraception, or overweight subjects available in the present study for formal statistical calculations and thus to draw binding conclusions, the analysis performed pointed out to some interesting trends: cigarette smoking seems to increase the 13 the opposite, overweight people may have a higher cumulative 13 C output with the 13 C-MBT, and finally gender does not exert any effect thereon.…”

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“…Indeed, subjects who participated in our study were all males to avoid interruption of fasting observed in women during menstruation, and also avoid any drug interaction with oral contraceptives that cause decreased clearance antipyrine 15 .…”