DIFFERENT PHARMACOKINETICS OF THYL-6-OXO-1,2,5-(3-C-14)DITHIAZOCINE-4-CARBOXYLIC ACID BETWEEN THE FASTING AND NONFASTING RAT - ROLE OF INTESTINAL MICROORGANISMS

1. We report differences in the pharmacokinetics of -delta-oxo-1,2,5-( 3-C-14)dithiazocine-4-carboxylic acid (C-14-SA3443) between the normal fasting and non-fasting rat, especially in the blood concentration-ti me curves and respiratory excretion. Exhalation of (CO2)-C-14 was an i mportant route of elimination and accounted for 21.2 % of the dose in the non-fasting rat but only 37 % in fasting animals. 2. In the intest inal microorganism-compromised rat, we found little differences in the pharmacokinetics of C-14-SA3443 between fasting and non-fasting state s. No respiratory excretion was observed in the intestinal microorgani sm-compromised animal. 3. In the reaction mixture of C-14-SA3443 with the cecal contents of rat, C-14-acetic acid and C-14-butyric acid were detected and (CO2)-C-14 barely detected. 4. The amounts of C-14-aceti c acid and C-14-butyric acid in the reaction mixture of C-14-SA3443 wi th non-fasting rat cecal contents were more than those with fasting ra t cecal contents. 5. We concluded that the reason for the different ph armacokinetics of C-14-SA3443 between the fasting and non-fasting rat was the differences in participation of the metabolism of C-14-SA3443 by intestinal microorganisms.