Increased theophylline metabolism in the menstrual phase of healthy women

J Allergy Clin Immunol. 1997 Jul;100(1):39-43. doi: 10.1016/s0091-6749(97)70192-1.


Background: We previously reported on a Japanese woman with premenstrual asthma whose serum theophylline concentration was lower before the onset of her menstrual period. We evaluated the clearance of theophylline in each phase of her menstrual cycle and found an increase in clearance in the premenstrual and menstrual phases.

Objective: This study was designed to investigate whether changes in theophylline clearance may occur with the menstrual cycle in nonasthmatic women.

Methods: Aminophylline, 250 mg, was infused intravenously for 45 minutes, and the clearance of theophylline was calculated in seven healthy, ovulatory women on days 1 or 2, 10, and 20 or 25 of the menstrual cycle. The serum concentration of theophylline was determined with an enzyme immunoassay (homogeneous).

Results: Theophylline clearance was significantly higher and its half-life was significantly shorter in the menstrual phase than in the follicular phase.

Conclusion: The metabolism of theophylline, and consequently, its clearance were increased in healthy women around the onset of menses. Clinicians must therefore consider the menstrual variation in theophylline metabolism when prescribing this drug to female patients.

MeSH terms

  • Adult
  • Aminophylline / administration & dosage
  • Aminophylline / pharmacokinetics
  • Female
  • Follicular Phase / metabolism
  • Half-Life
  • Humans
  • Infusions, Intravenous
  • Luteal Phase / metabolism
  • Menstrual Cycle / blood
  • Menstrual Cycle / metabolism*
  • Theophylline / blood
  • Theophylline / pharmacokinetics*


  • Aminophylline
  • Theophylline