INFLUENCE OF ORAL-CONTRACEPTIVE USE AND CIGARETTE-SMOKING, ALONE AND TOGETHER, ON ANTIPYRINE PHARMACOKINETICS

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: II cigarette smokers using low-dose oral contracept ives (n = 15); 2) nonsmokers using low-dose oral contraceptives (n = 1 2); 3) cigarette smokers not using oral contraceptives (n = 10); and 4 ) controls, neither cigarette smokers nor oral contraceptive users. Pl asma antipyrine concentrations during 24 to 48 hours after dosage were measured by highperformance liquid chromatography. Mean kinetic varia bles in the nonsmoking, nonoral contraceptive using control group were : volume of distribution, 37.7 L; elimination half-life, 13.2 hours; a nd clearance, 34.4 mL/min. In cigarette smoking, non-oral contraceptiv e 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 (e limination 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 eac h other when combined in humans.