Pharmacokinetics of theophylline in beagle dogs and asthmatic patients after multiple oral doses of sustained-release theophylline tablet formulation.

The bioavailability and pharmacokinetics of theophylline after a single intravenous administration of theophylline and multiple oral administration of a sustained-release theophylline tablet formation were studied in dogs. In addition, the pharmacokinetics of theophylline after multiple oral doses of the drug was also studied in asthmatic patients. In the intravenous administration of theophylline (5 mg/kg) to dogs, the theophylline half-life was 4.0 +/- 0.2 h. The apparent volume of distribution (Vd) and plasma theophylline clearance (CL) were 0.734 +/- 0.019 l/kg and 126.7 +/- 3.4 ml/kg/h, respectively. In the multiple oral doses of the drug in amounts ranging from 7.52 to 9.09 mg/kg, the Vd and CL were 0.765 +/- 0.021 l/kg and 111.0 +/- 2.4 ml/kg/h, respectively. The mean oral absorption rate constant (ka) was calculated to be 0.355 +/- 0.035 h-1 and the mean elimination rate constant (kel) was 0.146 +/- 0.007 h-1. The absolute bioavailability of the drug calculated by a computer fitting method was 1.08 +/- 0.07. The result suggests that the drug has complete absorption. On the other hand, the pharmacokinetic parameters in the asthmatic patients were 0.337 +/- 0.055 l/kg for the Vd, 32.55 +/- 3.48 ml/kg/h for the CL, 0.222 +/- 0.058 h-1 for the ka and 0.105 +/- 0.016 h-1 for the kel, respectively. This study indicated that the dog may be useful to predict bioavailability of a sustained-release theophylline tablet formulation in humans. However, it showed that there are differences between dogs and humans in the pharmacokinetic parameters.