Antipyrine metabolism during the menstrual cycle

Two studies were initiated to determine the effect of the menstrual cycle on antipyrine metabolism. In the first study a relatively large oral dose of antipyrine (15 mg/kg) was given on days 3, 5, 10, 14, 16, 20, and 25 after the onset of menstruation. Salivary antipyrine half‐lifes (t½s) declined progressively, suggesting that the long‐term administration of this dose had stimulated antipyrine metabolism. To minimize this possible induction, in the second study a much smaller dose of antipyrine (1 mg/kg) was given on the same days of the cycle as in the first study. There was no induction. In both experiments, the menstrual cycle had little or no effect on the mean salivary t½, mean metabolic clearance rate, or apparent volume of distribution of antipyrine. In the second, men served as controls. The mean kinetic parameters for the men did not differ from those for the women. Although individuals of each sex varied from day to day in each kinetic parameter, the magnitude of the intraindividual variability in antipyrine metabolism was the same for both. The mean intraindividual coefficient of variation for antipyrine t½s was 14.4 ± 1.6% (SE) in women and 12.4 ± 1.3% (SE) in men. No consistent pattern for either sex was observed in the day‐to‐day variations in the means of the kinetic parameters investigated. Several women in whom the t½ rose or fell at midcycle were found to have a different pattern when reexamined 6 mo later. Clinical Pharmacology and Therapeutics (1980) 28, 384–391; doi: 10.1038/clpt.1980.177