CEFTRIAXONE (CTX) KINETICS AND CEREBROSPINAL FLUID (CSF) CONCENTRATIONS IN INFANTS AFTER LOADING (LD) AND MAINTENANCE DOSES (MD)

Abstract

Thirteen infants (0.4-1.4 yrs) with meningitis were studied. CTX therapy consisted of a 75 mg/kg LD, followed by 50 mg/kg MD every 12 hrs IV over 10 minutes. Simultaneous blood and CSF samples were obtained in 11 infants at 11.5-12.8 hr after LD. In 3 of these, multiple blood samples were collected after the LD and after 9-10 days of MD; simultaneous blood and CSF samples were also collected at 1.25-5.75 hr at steady-state. CTX was measured by HPLC. Simultaneous serum and CSF concentration ranged from 10.5-40.3 and 1.8-8.0 μg/ml after the loading dose and 74-139 and 5.8-7.9 μg/ml at steady-state, respectively. After LD and at steady-state, CTX total clearance was 1.06±0.18 and 0.64±0.06 ml/min/kg (P<0.05), distribution volume was 0.33±0.06 and 0.26±0.06 L/kg and elimination half-life was 3.67±0.06 and 4.61±0.28 hr, respectively. A higher CTX clearance at higher dose may be partly due to concentration-dependent plasma protein binding of CTX reported in adults. Although the CSF/serum concentration was low, the CSF bactericidal titers exceeded 1:512 suggesting a great potential for CTX therapy of central nervous system infections due to susceptible organisms.