Disposition of cefixime in the material-fetal unit after an i.v. dose to pregnant rats

Cefixime, a potent, broad spectrum oral cephalosporin, is currently undergoing clinical trials. To determine the extent of transfer of cefixime across the placenta to the fetus, a single dose of 17.8 mg/kg 14C-cefixime was administered to rats on day 18 of gestation via the caudal vein. Maternal serum and urine, fetal plasma and tissues, and placentae were sampled at appropriate times after dosing. Separate rats were subjected to whole body autoradiography. The half-life for elimination of radioactivity from both maternal serum and placentae was 6.9 hours. Elimination from fetal plasma and tissues was somewhat longer, 12.5 and 13.7 hours, respectively. However, based on a comparison of area under the curve, relative to maternal dose, exposure of the fetuses to cefixime was far less than that of placentae. Peak radioactivity in fetal plasma occurred at 2 hours and was less than 2% of the maternal peak at 0.5 hours after dosing. Whole body autoradiography showed the greatest radioactivity in maternal liver, kidney and intestines. Somewhat less radioactivity appeared in placentae and virtually none could be visualized within the amniotic sac. Overall, the data indicate that exposure of the rat fetus to cefixime after a single maternal dose is limited by the placenta