THEOPHYLLINE METABOLISM IN HEALTHY NONSMOKERS AND IN PATIENTS WITH INSULIN-DEPENDENT DIABETES-MELLITUS

This study examined the pharmacokinetics of theophylline and formation of its metabolites in patients with insulin-dependent diabetes mellit us (IDDM) and in sex-, age-, and weight-matched healthy nonsmokers (n = 8 per group). Subjects received a single dose of 5 mg/kg theophyllin e intravenously. The pharmacokinetic parameter values of theophylline (plasma clearance, elimination half-life, and volume of distribution) and the formation clearance of theophylline metabolites (3-methylxanth ine, 1-methyluric acid, and 1,3-dimethyluric acid) were similar betwee n the two groups. Plasma free fraction of theophylline was higher in t he subjects with diabetes than in the healthy subjects (0.61 +/- 0.04 versus 0.56 +/- 0.02; P < 0.001). In the group of subjects with diabet es, there was a positive correlation between hemoglobin A(1c) values a nd plasma theophylline clearance (r = 0.76; p < 0.05), formation clear ance of 1,3-dimethyluric acid (r = 0.78; P < 0.05), and formation clea rance of 1-methyluric acid (r = 0.71; p < 0.05). These results suggest that patients with IDDM and poor glycemic control are moire likely to have an increased rate of theophylline metabolism.