Abstract
The pharmacokinetics of theophylline and its metabolites were studied in 13 patients with cystic fibrosis (CF) after an intravenous bolus of aminophylline (6 mg/kg) followed by multiple dosing with sustained release theophylline (Theo-Dur®) (7.7-14.8 mg/kg/day). An agematched group of 18 healthy subjects, taking a single oral dose of theophylline (300 mg), was used as a control group for comparing theophyline pharmacokinetic parameters. Literature values were used for the pharmacokinetics of the theophylline metabolites in normal subjects. Serum and urine concentrations of theophylline and its three main metabolites [3 methylxanthine (3MX), 1 methyluric acid (1MU), and 1,3 dimethyluric acid (1,3DMU)] were assayed by HPLC. The total body clearance and volume of distribution were significantly greater (p<0.01) in patients with CF than in control subjects. The steady-state serum concentration of 1 MU was greater in patients with CF than previously reported in normals. CF patients also had a lower plasma protein binding of theophylline. The symptomatic intolerance of theophylline in patients with CF may be related to an accumulation of this metabolite or a greater free fraction of theophylline or both.
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