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Theophylline metabolism in healthy nonsmokers and in patients with insulin‐dependent diabetes mellitus
Author(s) -
Korrapati Madhu R.,
Vestal Robert E.,
Loi ChoMing
Publication year - 1995
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/0009-9236(95)90210-4
Subject(s) - theophylline , volume of distribution , pharmacokinetics , glycemic , diabetes mellitus , medicine , endocrinology , insulin , chemistry , pharmacology
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 non‐smokers ( 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 A 1c 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. Clinical Pharmacology & Therapeutics (1995) 57 , 413–418; doi: