Pharmacokinetics of a modified, compounded theophylline product in dogs

Theophylline is a commonly used bronchodilator drug for treatment of chronic canine bronchitis, but no formulations validated in dogs are currently available. An oral, modified and compounded theophylline product (MCT), which could fulfil this need, is available through a USP-compliant, veterinary compounding pharmacy; however, its pharmacokinetic properties are unknown. The aim of this study was to determine the pharmacokinetics of MCT. Plasma drug concentrations were measured in seven healthy, fed dogs after single doses of intravenous aminophylline (8.6 mg/kg theophylline equivalent) and oral MCT (10 mg/kg). Systemic bioavailability of the MCT was 96.2 ± 32.9%. MCT times to maximum concentration, mean absorption time and terminal half-life were 8.85 ± 3.63, 6.95 ± 3.42, and 8.67 ± 1.62 hr, respectively. Based on simulations of 10 mg/kg and 12-hr dosing, steady-state plasma theophylline concentrations are expected to exceed the minimum therapeutic concentration for 71.7 ± 35.6% of the dosing interval. Overall, the MCT product investigated showed similar pharmacokinetic characteristics compared to previously validated extended-release theophylline products. An oral dose of 10 mg/kg q 12 hr is likely an appropriate dosage to begin therapy; however, therapeutic drug monitoring may be warranted because of inter-individual variation.