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 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.
Korrapati
M R
MR
Clinical Pharmacology and Gerontology Research Unit, Department of Veterans Affairs Medical Center, Boise, Idaho 83702, USA.
Vestal
R E
RE
Loi
C M
CM
D000328:Adult; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000208:ethnology / Q000378:metabolism*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007198:Indians, North American; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D012044:Regression Analysis; D013806:Theophylline / Q000493:pharmacokinetics*
D006442:Glycated Hemoglobin; D013806:Theophylline