Pharmacokinetics of vephylline--a new N-substituted theophylline derivative

Vephylline (7,2-bis-2-hydroxyethylamino-1, 3-dimethylxanthine tartarate) is a xanthine derivative with high bronchodilating activity, low toxicity, and weak effects on the central nervous system. The aim of this study is to determine the pharmacokinetic parameters of vephylline after intravenous and oral (in solution and in tablets) administration to rabbits. Vephylline (dose 50 mg/kg b.w. intravenousely and orally in solution and dose 53.5 mg/kg b.w. in the form of tablets) is administered to the rabbits in an autocontrol crossover design at 7-days intervals. After the intravenous administration the distribution is relatively fast (t1/2 alpha = 3.28h). High values of the apparent volume of distribution--12.15 1/kg suggest tissue accumulation. Elimination is considerably slower (t1/2 beta = 19,00 h) than distribution. After oral administration of the drug in solution the absorption half-life is short and the bioavailability is relatively high. Peak plasma levels are attained at the first hour. The differences in the distribution and elimination patterns for vephylline and theophyline could determine a longer effect for the new bronchodilating drug. The results are discussed in regard to the future clinical application of vephylline.