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Ceftazidime pharmacokinetics in preterm infants: effects of renal function and gestational age
J N van den Anker1, R C Schoemaker, W C Hop
1Department of Pediatrics and Epidemiology, Erasmus University, Rotterdam, The Netherlands.
Insights
Ceftazidime dosing in preterm infants should consider gestational age and glomerular filtration rate (GFR). Adjustments are necessary for infants exposed to indomethacin, ensuring optimal antibiotic levels.
Area of Science:
- Neonatal Pharmacology
- Pediatric Nephrology
- Antibiotic Pharmacokinetics
Background:
- Ceftazidime is a crucial antibiotic for treating infections in preterm infants.
- Understanding its pharmacokinetic profile in this vulnerable population is essential for effective therapy.
- Gestational age and renal function significantly influence drug disposition in neonates.
Purpose of the Study:
- To investigate the impact of gestational age on ceftazidime pharmacokinetics in preterm infants.
- To correlate these pharmacokinetic changes with glomerular filtration rate (GFR).
- To develop evidence-based dosage recommendations for ceftazidime in preterm neonates on day 3 of life.
Main Methods:
- Pharmacokinetic analysis of multiple ceftazidime doses in 136 preterm infants.
- Serum samples analyzed using HPLC for ceftazidime concentrations.
- Glomerular filtration rate (GFR) assessed via 24-hour continuous inulin infusion.
Main Results:
- Ceftazidime clearance and volume of distribution increased with gestational age and GFR.
- Serum half-life and trough levels decreased with increasing gestational age.
- Prenatal indomethacin exposure was linked to reduced GFR and ceftazidime clearance.
Conclusions:
- Ceftazidime dosage recommendations for preterm infants should incorporate gestational age and GFR.
- Dosage adjustments are crucial for preterm infants with prenatal indomethacin exposure.
- Optimizing ceftazidime therapy ensures therapeutic drug levels and improves patient outcomes.
Objective:
The objectives of this study were (1) to determine the effects of gestational age on ceftazidime pharmacokinetics in the preterm infant, (2) to relate these effects to changes in glomerular filtration rate (GFR), and (3) to establish appropriate dosage recommendations for preterm infants on day 3 of life.
Methods:
Multiple-dose pharmacokinetics of ceftazidime (administered twice daily in a 25 or 50 mg/kg body weight intravenous dose) were evaluated in 136 preterm infants on day 3 of life. Blood samples were collected from an arterial catheter 0, 1/2, 1, 2, 4, 8, and 12 hours after the intravenous dose. An HPLC method was used to determine ceftazidime concentrations in serum. The GFR was studied simultaneously by means of the 24-hour continuous inulin infusion technique.
Results:
The total body clearance, volume of distribution, and elimination serum half-life of ceftazidime (mean +/- SD) were 55.7 +/- 34.4 ml/hr (37.3 +/- 11.9 ml/hr/kg), 496 +/- 228 ml (350 +/- 96 ml/kg), and 6.95 +/- 2.32 hours, respectively. The mean +/- SD peak and trough levels were 114.9 +/- 39.4 and 33.9 +/- 17.8 mg/L. All infants had a serum trough level above 5 mg/L. Clearance and volume of distribution of ceftazidime and GFR increased significantly with increasing gestational age, whereas serum trough levels and serum half-life of ceftazidime decreased significantly with increasing gestational age. Ceftazidime clearance increased significantly with increasing GFR. Prenatal exposure to indomethacin resulted in significantly lower GFR values and ceftazidime clearances.
Conclusions:
Dosage recommendations for ceftazidime administration in preterm infants during the first week of life should be based on gestational age and GFR. Additional adjustments in dosage are indicated in preterm infants who are exposed prenatally to indomethacin.