This study was undertaken to determine plasma levels, metabolism, urinary excretion of propentofylline after intravenous (i. v.) and oral (p. o.) administration of 3 mg/kg to rabbits.
Following i. v. administration the plasma level of the unchanged propentofylline declined rapidly in a biphasic manner with the half-lives of α- and β-phases of 4.6 and 21.4 min, respectively. The major plasma components were acid (carboxyl) metabolites A80 2751 and A80 2831 and a hydroxyl metabolite A72 0287. Only small amounts of hydroxyl metabolites A79 2442 and A79 2438 were detected. In the plasma, after p. o. administration the parent compound was not found and only the above 2 acid metabolites were present at high concentrations. The ratio of p. o. to i. v. AUCs combined for the 2 acid metabolites was approximately 0.9, suggesting that propentofylline was well absorbed from the gastrointestinal tract.
A80 2751, A80 2831, and A79 2438, mainly the former 2 acid metabolites, accounted for nearly 100 % of the total urinary excretion following i. v. and p. o. administration; the excretion of the parent compound to the urine was minimal. No conjugates were present in the urine. The urinary recovery within 48 hr was about 23 and 26 % of the given dose after i. v. and p. o. administration, respectively.