Related Experiment Videos
Population pharmacokinetics of ceftizoxime in premature newborns
Insights
Population pharmacokinetics of ceftizoxime in premature neonates indicate that a weight-based dosing regimen of 25 mg/kg every 12 hours is appropriate for treating suspected sepsis.
Area of Science:
- Pharmacology
- Neonatal Medicine
- Clinical Pharmacy
Background:
- Sepsis is a serious concern in premature newborns.
- Ceftizoxime is an antibiotic used to treat bacterial infections.
- Understanding ceftizoxime pharmacokinetics in neonates is crucial for effective dosing.
Purpose of the Study:
- To determine the population pharmacokinetic parameters of ceftizoxime in premature infants.
- To evaluate the appropriateness of a specific ceftizoxime dosing regimen in this population.
Main Methods:
- Population pharmacokinetic analysis using NONMEM.
- Study involved 50 premature newborns (<1 week old) with suspected sepsis.
- Serum ceftizoxime concentrations were measured using HPLC after multiple intravenous doses.
Main Results:
- Final pharmacokinetic parameter estimates: clearance 27.1 ml/h/kg, volume of distribution 333 ml/kg, half-life 8.5 h.
- Gestational and postnatal age did not significantly affect ceftizoxime clearance.
- Variability in clearance decreased from 80% to 50% with weight-based dosing.
Conclusions:
- The dosing regimen of 25 mg/kg ceftizoxime every 12 hours is suggested as appropriate for premature neonates.
- Weight-based dosing is recommended to manage the variability in ceftizoxime clearance.
- This regimen supports effective treatment of suspected sepsis in this vulnerable population.
Abstract:
The population pharmacokinetic parameters of ceftizoxime were determined in 50 premature newborns less than 1 week of age (birth weight = 1.8 +/- 0.6 kg) with a clinical diagnosis of suspected sepsis. Each infant received ceftizoxime 25 mg/kg every 12 h intravenously over 30 min for a total of 6 doses. Serum concentrations of ceftizoxime were assayed by HPLC at 0.5, 1, 2.5 and 11.5 h or at 0.5, 1.5, 4.5 and 11.5 h after the first and the sixth dose. A total of 184 serum concentrations following the first dose and 160 following the sixth dose were fit separately and then collectively to a one-compartment model using NONMEM. The separately estimated parameters were not significantly different between the first and the sixth dose. The final parameter estimates were 27.1 ml/h/kg, 333 ml/kg and 8.5 h for clearance, volume of distribution and half-life, respectively. Other factors including gestational and postnatal age were not associated with alterations in ceftizoxime clearance. That the large variability in clearance was decreased from a coefficient of variation of 80 to 50% warrants dosing premature infants on the basis of body weight. The results of this study suggest that 25 mg/kg ceftizoxime every 12 h appears to be an appropriate dosing regimen for premature neonates.