The pharmacokinetic disposition of theophylline was determined by high‐performance liquid chromatographic analysis of plasma samples from six healthy, adult horses following the administration of intravenous aminophylline (dosed at 9.94 mg/kg as theophylline), immediate‐release aminophylline tablets (dosed at 9.94 mg/kg as theophylline), and sustained‐release theophylline tablets (dosed at 20 mg/kg). The elimination rate constant (Λz), apparent volume of distribution (Vz), and clearance (Cl) determined by compartmental analysis of the intravenous data were 0.07 ± 0.01 h‐1, 0.80 ± 0.06 l/kg, and 0.06 ± 0.01 l/kg/h (mean ± SD), respectively. Mean residence time determined by statistical moment theory of the oral data was different (P < 0.05) for the immediate‐release aminophylline (13.8 ± 2.8 h) and sustained‐release theophylline (18.2 ± 2.3 h) formulation. Immediate‐release aminophylline tablets quickly achieved peak theophylline plasma concentrations of 11.51 ± 1.4 μg/ml at 1–6 ± 0.6 h while the sustained‐release theophylline tablets were more slowly absorbed and achieved peak theophylline concentrations of 17.20 ± 1.3 μg/ml at 7.3 ± 1.0 h. Absolute bioavailability was 87% for the immediate‐release and 97% for the sustained‐release formulation. Using the principle of superposition, a loading dose of 20 mg/kg of the sustained‐release formulation followed by maintenance doses of 15 mg/kg every 24 h was predicted to achieve trough–peak theophylline plasma concentrations between 6 and 17 μg/ml.
|Original language||English (US)|
|Number of pages||9|
|Journal||Journal of Veterinary Pharmacology and Therapeutics|
|State||Published - Dec 1989|
ASJC Scopus subject areas