The pharmacokinetic studies of cephalothin, cefazolin and cefmetazole in the neonates and the premature babies.

Abstract

The pharmacokinetic study of antibiotics provides essential information for the rational antibiotic therapy of infections in children and especially in neonates. It is therfore necessary to establish techniques to measure the plasma concentrations of antibiotics, using small volumes. Preliminary studies in rabbits and the further studies in the neonates and in older children showed excellent correlation between the concentration of plasma antibiotics in venous and capillary blood, as measured by High Pressure Liquid Chromatography (HPLC) and by the bioassay. We confirmed that the HPLC is more useful for assays, in neonates and children for the following reasons; the volume of the plasma is less than standard bioassay (50 μl vs 200 μl); less time is required (20 min vs 18-20 hrs) ; the method can detect the metabolites; multiple antibiotics can be assayed simultaneously. Pharmacokinetic studies for cephalothin (CET), cef azolin and cef metazole in neonates (2-21 days) and in older children (9-12 years) using bioassay and HPLC showed that these antibiotics had more prolonged half-lives and delayed urinary excretion in neonates than in older children. Desacetylcephalothin (DACET), the metabolite of CET, was detected in both plasma and urine in neonates as well as in older children. The amount of urinary DACET, however, was larger in neonates than in older children, and the half-life of DACET was longer in neonates than in older children.