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Pharmacokinetics of cefotaxime in preterm infants
J B Gouyon1, A Pechinot, C Safran
1Department of Pediatrics, University of Bourgogne, Dijon, France.
Insights
Pharmacokinetic profiles of cefotaxime (CTX) and its metabolite desacetylcefotaxime (DCTX) were studied in preterm infants. CTX serum concentrations remained above bactericidal levels for 12 hours, with half-life influenced by gestational age.
Area of Science:
- Neonatal pharmacology
- Pediatric pharmacokinetics
- Antibiotic drug monitoring
Background:
- Neonatal infections require careful antibiotic dosing.
- Cefotaxime is a commonly used antibiotic in neonates.
- Understanding cefotaxime pharmacokinetics is crucial for optimizing treatment in preterm infants.
Purpose of the Study:
- To determine the pharmacokinetic parameters of cefotaxime (CTX) and its metabolite desacetylcefotaxime (DCTX) in preterm infants.
- To assess if cefotaxime serum concentrations remain above the mean bactericidal concentration for neonatal pathogens.
- To investigate the relationship between gestational age and cefotaxime pharmacokinetics.
Main Methods:
- Pharmacokinetic analysis of cefotaxime and desacetylcefotaxime in 10 preterm infants (28-37 weeks gestation).
- Blood samples collected over 12 hours post-infusion and analyzed using high-performance liquid chromatography.
- Dosing regimen: 25 mg/kg cefotaxime twice daily.
Main Results:
- Cefotaxime serum concentrations remained above the mean bactericidal concentration for 12 hours post-infusion.
- Mean elimination half-life of CTX was 3.68 ± 1.48 hours.
- Significant inverse relationship observed between gestational age and elimination half-life and AUC of both CTX and DCTX.
Conclusions:
- Cefotaxime dosing of 25 mg/kg twice daily maintains therapeutic concentrations in preterm infants.
- Gestational age is a significant factor influencing cefotaxime and desacetylcefotaxime pharmacokinetics.
- Further studies may refine cefotaxime dosing strategies based on gestational age in preterm neonates.
Abstract:
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 (AUC0-12 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 micrograms/ml/h (170-867), respectively. The AUC0-12 h for DCTX was 170 +/- 93 micrograms/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.