PHARMACOKINETICS OF CEFOTAXIME IN PRETERM INFANTS

Pharmacokinetic parameters of cefotaxime (CTX) and its metabolite desacetylcefotaxime (DCTX) were assessed on the 3rd day of treatment in 10 preterm infants (28-37 weeks gestation) aged 3-8 days and receiving 25 mg/kg CTX twice daily. Blood samples were collected from an umbilical artery catheter at 0, 0.08, 0.25, 0.5, 0.75, 1, 2, 4, 8, 12 h after a short peripheral infusion (5 min) and were assayed by high-performance liquid chromatography. During the 12 h following the CTX infusion, serum concentrations of CTX remained above the mean bactericidal concentration for pathogens commonly isolated during the neonatal period. The mean (± SD) elimination half-life, volume of distribution, total body clearance and area under the serum concentration-time curve (AUC(0-12 h)) for CTX were: 3.68 ± 1.48 h (range: 1.89-6.82), 431 ± 149 ml/kg (219-636), 1.57 ± 0.80 ml/kg/min (0.60-3.27) and 373 ± 206 μg/ml/h (170-867), respectively. The AUC(0-12 h) for DCTX was 170 ± 93 μg/ml/h (61-374). A significant inverse relationship was found between gestational age and the elimination half-life of CTX, and the AUC of both CTX and DCTX.