Comparison of the pharmacokinetics of five beta-lactam antibiotics between neonatal and adult rats.

The pharmacokinetics of beta-lactam antibiotics in adult and neonatal rats were compared after their intravenous or oral administration. The distribution volumes of cefazolin, cefamandole and cefmetazole were larger for the neonatal than the adult rats, whereas the distribution volumes of cephradine and cephalexin were smaller for the neonates. Neonatal rats showed lower clearances than adults for all antibiotics tested. The maximum plasma concentrations (Cmax) after oral administration of cefazolin, cefamandole and cefmetazole were significantly higher (3-15 times) for neonatal than for adult rats. However, in the case of cephradine and cephalexin, the increase of Cmax for neonatal rats was small. The absolute bioavailabilities for cefazolin, cefamandole and cefmetazole were significantly larger in the neonates. Thus, cefazolin, cefamandole and cefmetazole, which were poorly absorbed by adults, were found to be easily absorbed by the intestines of neonatal rats.