Related Experiment Videos
Ceftazidime pharmacokinetics in preterm infants: effect of postnatal age and postnatal exposure to indomethacin
J N van den Anker1, W C Hop, R C Schoemaker
1Department of Pediatrics, Erasmus University, Netherlands.
Insights
Postnatal age significantly alters ceftazidime (CAZ) pharmacokinetics in preterm infants, necessitating dosage adjustments after the first week. Indomethacin exposure reduces these changes, impacting CAZ dosing strategies.
Area of Science:
- Neonatal pharmacology
- Pediatric pharmacokinetics
- Antibiotic dosing
Background:
- Preterm infants exhibit immature organ systems affecting drug metabolism.
- Ceftazidime (CAZ) is a crucial antibiotic for treating infections in neonates.
- Understanding pharmacokinetic changes with postnatal development is vital for safe and effective therapy.
Purpose of the Study:
- To investigate the impact of postnatal age and indomethacin exposure on ceftazidime pharmacokinetics in preterm infants.
- To determine optimal ceftazidime dosing regimens based on infant age and medication history.
Main Methods:
- Pharmacokinetic analysis of ceftazidime in 23 preterm infants on days 3 and 10 post-birth.
- Intravenous administration of ceftazidime (25 mg/kg) with serial blood sampling.
- Glomerular filtration rate (GFR) assessment using 24-hour inulin infusion.
Main Results:
- Ceftazidime clearance and GFR significantly increased from day 3 to day 10.
- Volume of distribution and elimination half-life of ceftazidime significantly decreased with age.
- Indomethacin exposure attenuated the age-related pharmacokinetic changes.
Conclusions:
- Ceftazidime dosage requires adjustment after the first week of life in preterm infants.
- Indomethacin-exposed infants may require different dosing adjustments due to altered ceftazidime pharmacokinetics.
- Individualized dosing strategies considering postnatal age and indomethacin use are recommended.
Abstract:
1. The effects of postnatal age and postnatal exposure to indomethacin on the pharmacokinetic parameters of ceftazidime (CAZ) were investigated in 23 preterm infants (gestational age 28.7 +/- 1.7 weeks; weight 1086 +/- 311 g) on day 3 and day 10 after birth. 2. CAZ (25 mg kg-1) was administered by intravenous bolus injection. Blood samples were drawn from an arterial catheter at 0, 0.5, 1, 2, 4, 8, and 12 h after the dose and CAZ concentrations in serum were determined by h.p.l.c. CAZ pharmacokinetics followed a one-compartment open model. 3. The glomerular filtration rate (GFR) of all infants was studied by means of the 24 h continuous inulin infusion technique. 4. The total body clearance of CAZ (34.7 +/- 9.2 vs 50.6 +/- 19.6 ml h-1, P < 0.05; 30.7 +/- 5.9 vs 41.6 +/- 9.0 ml h-1 kg-1, P < 0.05) and GFR (0.72 +/- 0.11 vs 0.91 +/- 0.15 ml min-1, P < 0.05) increased, whereas the apparent volume of distribution (425 +/- 147 vs 352 +/- 108 ml, P < 0.05; 363 +/- 59 vs 292 +/- 44 ml kg-1, P < 0.005) and the elimination half-life (8.7 +/- 2.8 vs 5.0 +/- 0.9 h, P < 0.005) decreased significantly between day 3 and day 10 after birth. Clearance of CAZ increased with increasing GFR (r = 0.81, P < 0.001). 5. In infants with postnatal exposure to indomethacin the changes in CAZ pharmacokinetics were markedly reduced. 6. These results indicate that the dosage regimen of CAZ should be adjusted after the first week of life except in infants who were postnatally exposed to indomethacin.