Theophylline metabolism in healthy nonsmokers and in patients with insulin-dependent diabetes mellitus.

Abstract

This study examined the pharmacokinetics of theophylline and formation of its metabolites in patients with insulin-dependent diabetes mellitus (IDDM) and in sex-, age-, and weight-matched healthy nonsmokers (n = 8 per group). Subjects received a single dose of 5 mg/kg theophylline intravenously. The pharmacokinetic parameter values of theophylline (plasma clearance, elimination half-life, and volume of distribution) and the formation clearance of theophylline metabolites (3-methylxanthine, 1-methyluric acid, and 1,3-dimethyluric acid) were similar between the two groups. Plasma free fraction of theophylline was higher in the 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 diabetes, there was a positive correlation between hemoglobin A1c values and plasma theophylline clearance (r = 0.76; p < 0.05), formation clearance of 1,3-dimethyluric acid (r = 0.78; p < 0.05), and formation clearance of 1-methyluric acid (r = 0.71; p < 0.05). These results suggest that patients with IDDM and poor glycemic control are more likely to have an increased rate of theophylline metabolism.