[Studies on absorption, distribution and excretion of 14C labeled pivaloyloxymethyl (+)-(6R,7R)- 7-[(Z)-2-(2-amino-4-thiazolyl)-2-methoxyiminoacetamido]- 3-[(5-methyl-2H-tetrazol-2-yl)methyl]-8-oxo-5-thia- 1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate (14C-T-2588) in rats and mice].
Absorption, distribution and excretion of T-2588 were studied in rats and mice using (aminothiazole-2-14C) T-2588 and (pivaloyloxymethyl-14C) T-2588. Results are summarized below. The binding rate of 14C-T-2525, an activated form of 14C-T-2588 in vivo, to serum protein was 90 approximately 100% in rats and mice after an oral administration of (aminothiazole-2-14C) T-2588. Blood levels of radioactivity reached to the highest concentration at 1 hour after an oral administration of (aminothiazole-2-14C) T-2588 to rats, and then gradually diminished. After an oral administration of (aminothiazole-2-14C) T-2588 to rats and mice, the highest radioactivity distribution was found in kidney among all the organs except stomach, intestine and bladder. Radioactivity was widely distributed into other organs such as adrenal, lung, liver, heart and pancreas. But little radioactivity was found in the brain. In new born rats, tissue levels of radioactivity were lower and diminished slower than those of adult rats. After an oral administration of (aminothiazole-2-14C) T-2588 to rats and mice, urinary excretion of radioactivity was about 26% and 35% of the dosed radioactivity in rats and mice, respectively, and fecal excretion was about 76% and 63% of the dosed radioactivity in rats and mice, respectively. Urinary and fecal excretion patterns of radioactivity after multiple oral administration of (aminothiazole-2-14C) T-2588 for 7 days to mice were similar to those after a single administration. This result suggests that T-2588 did not accumulate in the body. After an oral administration of (pivaloyloxymethyl-14C) T-2588 to rats and mice, urinary excretion was both about 8% of the dosed radioactivity, and fecal excretion was both about 6%. Then excretion of 14CO2 into respiratory air was about 55% and 66% of the dosed radioactivity in rats and mice, respectively. Biliary excretion was about 6.5% of the dosed radioactivity after an oral administration of (aminothiazole-2-14C) T-2588 to rats. Small amount of radioactivity was secreted to the milk after intravenous administration of (aminothiazole-2-14C) T-2525 to nursing rats. After an administration of (aminothiazole-2-14C) T-2588 to pregnant mice, radioactivity hardly transferred into the fetus.
D000284:Administration, Oral; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D015281:Cefmenoxime / Q000031:analogs & derivatives*; D002511:Cephalosporins / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000378:metabolism; D007408:Intestinal Absorption; D008297:Male; D008431:Maternal-Fetal Exchange; D051379:Mice; D011247:Pregnancy; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D014018:Tissue Distribution
D001798:Blood Proteins; D002511:Cephalosporins; C046817:cefteram pivoxil; D015281:Cefmenoxime