Pharmacokinetics and safety of ceftriaxone in the neonate.

The pharmacokinetics and safety of ceftriaxone were examined in 39 neonates who required antibiotics for clinically suspected sepsis. The drug was administered as a once daily dose of 50 mg/kg by the intravenous (IV) or intramuscular (IM) route. Ceftriaxone was assayed in 49 series of blood samples, 3 samples of cerebrospinal fluid (CSF) and 15 samples of urine by a microbiological technique. Blood was collected before, during and after treatment for biochemical analysis. Routine haematological investigations were also monitored. There was no significant difference between the maximum plasma concentrations following IV (153 +/- 39 mg/l) or IM (141 +/- 19 mg/l) administration (first dose). The mean elimination half-life, total body clearance, and volume of distribution following the first dose were 15.4 +/- 5.4 h, 0.28 +/- 0.12 ml/min per kg and 325 +/- 59 ml/kg respectively. Clearance increased with increasing postnatal age and body temperature (P less than 0.0002) and decreasing plasma creatinine concentration (P less than 0.005). Increasing plasma protein concentration was associated with a decrease in volume of distribution (P less than 0.001). There were no drug-associated changes in any of the biochemical or haematological parameters examined. Ceftriaxone is a safe and well tolerated antibiotic for use in the treatment of newborn sepsis and possibly meningitis. A once daily administration of 50 mg/kg by the IV and IM routes provides satisfactory plasma concentrations throughout the dosage interval whilst avoiding accumulation.