Pharmacokinetic disposition of an immediate‐release aminophylline and a sustained‐release theophylline formulation in the horse

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 (Λ_z), apparent volume of distribution (V_z), 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.