Effect of chronic oral contraceptive steroids on theophylline disposition.

The effect of chronic oral contraceptive (OC) usage on the disposition of theophylline was examined. Aminophylline solution (4 mg/kg) was given orally to 8 healthy female non-OC users and to 8 healthy women who were chronic (greater than 6 months) OC users. The OC user group had a significantly lower total plasma clearance of theophylline than women not using OC (35.1 +/- 5.6 vs. 53.1 +/- 14.5 ml/h/kg). The t1/2 was also significantly prolonged in the OC group (9.79 +/- 1.43 vs. 7.34 +/- 1.75 h) while the volume of distribution was similar between the 2 groups. The serum ethinylestradiol (EE) concentrations after oral OC administration were measured simultaneously. The apparent clearance of EE was about 30% lower in the OC users. A significant positive correlation was found between the apparent clearance of EE and the plasma clearance of theophylline. The effects of OC are predominantly due to chronic use with decreased elimination of both theophylline and EE.