Women Respond Differently to Theophylline than do Men

Abstract

Gender differences in drug response are well known and reflect important aspects of drug treatment. We treated 178 women and 134 men with smell loss in a clinical trial in which all patients received oral theophylline for 2‐8 months at daily doses of 200, 400, 600 and 800mg. At the end of each period smell function was measured by subjective responses and standard psychophysical techniques and plasma theophylline was measured by a fluorescence polarization method. Plasma theophylline was consistently higher among women than men at each theophylline dose and differences increased as theophylline dose increased: 200mg, men ‐ 3.6±0.2, women ‐ 4.4±0.3 mg/L (Mean±SEM); 400mg, men ‐ 4.0±0.4, women ‐ 10.2±0.7; 600mg, men ‐ 8.2±0.6, women ‐ 10.8±0.9; 800mg, men ‐ 9.6±0.8, women ‐ 12.5±0.7. Subjective smell improvement at 600 and 800mg in women was consistently higher than in men. Responses to psychophysical testing in women were consistently better than in men at 400, 600 and 800mg and were statistically significant after 600mg. These differences may relate to a relative decreased theophylline metabolic clearance rate in women than in men caused by gonadal hormone differences. The decreased clearance rate could cause slower drug absorption with increased drug blood and tissue levels resulting in a better response of their smell loss. This apparently is the first report of gender differences in theophylline blood levels.