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[Pharmacokinetic analysis of cefozopran in neonatal infections--population pharmacokinetics using nonmem]
Y Sakurai1, T Hishikawa, N Hiramatsu
1Pharmaceutical Development Division, Takeda Chemical Industries, Ltd.
Insights
Pharmacokinetic analysis of cefozopran (CZOP) in neonates revealed age-dependent elimination. Dosing adjustments are recommended for infants under 1 day old to ensure safety and efficacy.
Area of Science:
- Neonatal Pharmacology
- Antibiotic Pharmacokinetics
- Pediatric Drug Dosing
Background:
- Cefozopran (CZOP) is an antibiotic used in neonatal patients.
- Understanding its pharmacokinetic profile in neonates is crucial for safe and effective treatment.
- Previous data on CZOP pharmacokinetics in this vulnerable population is limited.
Purpose of the Study:
- To evaluate the pharmacokinetics, efficacy, and safety of cefozopran (CZOP) in neonatal patients.
- To develop population pharmacokinetic (PPK) models for CZOP in neonates.
- To determine optimal dosing strategies based on age and body weight.
Main Methods:
- Population pharmacokinetic (PPK) analysis of cefozopran (CZOP) concentrations in 42 neonatal patients.
- Development of predictive equations for clearance (CL) and volume of distribution (Vd) based on body weight (WT) and postnatal age.
- Evaluation of pharmacokinetic parameter variability.
Main Results:
- Cefozopran (CZOP) clearance (CL) and volume of distribution (Vd) were successfully modeled using body weight and postnatal age.
- CL = 0.0452 x WT^1.75 (postnatal age > 1 day); CL = 0.623 x 0.0452 x WT^1.75 (postnatal age ≤ 1 day); Vd = 0.455 x WT.
- CZOP elimination was approximately 38% lower in neonates ≤ 1 day old compared to older infants, indicating age-dependent pharmacokinetics.
Conclusions:
- Cefozopran (CZOP) elimination is significantly influenced by postnatal age in neonates.
- Dosing adjustments, particularly for the interval of administration, are necessary for neonates ≤ 1 day old.
- Further studies with larger cohorts are warranted to confirm these findings and refine dosing guidelines.
Abstract:
This report describes the results on pharmacokinetics, efficacy and safety of cefozopran (CZOP) in neonatal patients. Enrolled patients were 136 in total whose informed consents to enter this study had been given by their parents. Among them, blood samples were collected from 42 neonates to analyze concentrations of CZOP by population pharmacokinetics (PPK) methods. Based on this analysis, the average pharmacokinetic parameters of CZOP and the variabilities of them in different morbid pharmacological backgrounds and in different subjects were evaluated. This PPK analysis showed that clearance (CL) and distribution volume (Vd) of CZOP could be estimated by the following equations; CL = 0.0452 x WT1.75 (in the case of the postnatal age of over than 1 day) CL = 0.623 x 0.0452 WT1.75 (in the case of the postnatal age of 1 day or less) Vd = 0.455 x WT where WT indicates body weight in kg. The coefficients of variation among individual subjects on CL and Vd were found to be 20.7% and 20.0%, respectively. From this PPK analysis it was indicated that the elimination of CZOP is dependent on the postnatal age and is approximately 38% lower in the younger group than in the older group. Therefore, it could be concluded that, though the cases of evaluation were small in number, adjustment of dosing of CZOP is necessary, particularly in prolongation of intervals of administration, in cases of postnatal age of 1 day or less.