Kinetic and metabolic studies of 7-(1,3-dithiolan-2-ylmethyl)-1,3-dimethylxanthine in the rat

Abstract

The kinetics (absorption, tissue distribution and excretion) of 7-(1,3-dithiolan-2-ylmethyl)-1, 3-dimethylxanthine(ABC 99) were studied in the rat. ABC 99 was administered orally at doses of 10, 30 and 100 mg/kg for the serum kinetic studies. Only the 30 mg/kg dose was used for the tissue distribution and excretion kinetic studies. ABC 99 is rapidly absorbed, metabolized in the liver and partially excreted in the urine. It is equally distributed in the tissues, including the brain, although in much lower amounts than those absorbed. Three metabolites were identified: theophylline, which forms in very small quantities, and two isomers (cis and trans) of the sulfoxide. The latter two compounds form in larger amounts with respect to theophylline, and the trans-isomer predominates. The metabolites are distributed to the tissues, but do not accumulate. Elimination is virtually complete at 24 h. The pharmacological activity of ABC 99 (antibronchospastic, mucoregulatory and anti-inflammatory) can be attributed the compound, which is absorbed in its original form. Similar activity of the two sulfoxides (met 1 and 2) cannot be excluded at present as they have a structure analogous to ABC 99.