title: 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.
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Scavone
authors.forename: D J
authors.initials: DJ
authors.lastname: Greenblatt
authors.forename: D R
authors.initials: DR
authors.lastname: Abernethy
authors.forename: B G
authors.initials: BG
authors.lastname: Luna
authors.forename: J S
authors.initials: JS
authors.lastname: Harmatz
authors.forename: R I
authors.initials: RI
authors.lastname: Shader
mesh_terms: D000293:Adolescent; D000328:Adult; D000983:Antipyrine / Q000493:pharmacokinetics*; D003278:Contraceptives, Oral, Hormonal / Q000494:pharmacology*; D004347:Drug Interactions; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D012907:Smoking / Q000378:metabolism*
chemical_list: D003278:Contraceptives, Oral, Hormonal; D004958:Estradiol; D000983:Antipyrine