Related Experiment Videos
Influence of maturation and growth on cefetamet pivoxil pharmacokinetics: rational dosing for infants
W L Hayton1, J Kneer, R de Groot
1College of Pharmacy, Ohio State University, Columbus 43210-1291, USA.
Insights
This study characterized cefetamet pharmacokinetics in infants, finding oral absorption comparable to adults but longer plasma half-life and lower urinary recovery. A maturation model was developed for pediatric dosing guidelines.
Area of Science:
- Pharmacology
- Pediatric Medicine
- Drug Metabolism
Background:
- Infants often require antibiotic treatment for urological conditions.
- Understanding drug pharmacokinetics in infants is crucial for safe and effective dosing.
- Cefetamet pivoxil is an oral prodrug of cefetamet, an antibiotic used to treat bacterial infections.
Purpose of the Study:
- To characterize the pharmacokinetics of intravenous (i.v.) cefetamet and oral bioavailability of cefetamet pivoxil in infants.
- To develop a pharmacokinetic model for cefetamet clearance that accounts for maturation and growth in pediatric patients.
- To establish dosing regimen guidelines for pediatric patients aged 3.5 months and older.
Main Methods:
- Pharmacokinetic analysis of i.v. cefetamet and oral cefetamet pivoxil in hospitalized infants (3.5-17.3 months).
- Measurement of plasma concentrations, half-life, urinary recovery, volume of distribution, and systemic clearance.
- Development of a maturation-dependent pharmacokinetic model for cefetamet clearance.
Main Results:
- Oral cefetamet pivoxil absorption in infants was 38%, comparable to children and adults.
- Intravenous cefetamet had a plasma half-life of 3.03 hours in infants, longer than in older children.
- Urinary recovery of cefetamet was lower in infants (63.4%) compared to older individuals (80%).
- Systemic clearance was lower in infants due to immature processes, increasing 4.5-fold by age 5 due to maturation.
Conclusions:
- Cefetamet exhibits distinct pharmacokinetic properties in infants compared to older populations.
- A pharmacokinetic model incorporating maturation is essential for accurate pediatric dosing.
- The developed model provides a basis for establishing safe and effective cefetamet dosing regimens for infants and young children.
Abstract:
The pharmacokinetics of intravenous (i.v.) cefetamet and the bioavailability of oral cefetamet pivoxil in infants aged 3.5 to 17.3 months who were hospitalized for urological surgery were characterized. The absorption of cefetamet pivoxil administered in a syrup formulation was 38 +/- 19% (n = 5) for infants, which was comparable to values observed for children and adults. The plasma half-life of i.v. cefetamet was 3.03 +/- 0.96 h (mean +/- standard deviation; n = 20) in the infants. This was not different from the value observed for normal adult subjects but was longer than that reported for children aged 3 to 12 years. Urinary recovery of cefetamet after i.v. administration to infants was 63.4 +/- 17.7% (n = 16), which was less than the 80% recovery found in older children and adults. The steady-state volume of distribution was 399 +/- 116 ml/kg of body weight. It was comparable in size and showed the same dependence on body weight as it did in children and adults. The mean systemic clearance per kilogram of body weight in the infants was lower than that in children and adults, apparently because of immaturity of clearance processes. A model that accounted for maturation and growth with increasing age was developed for the clearance. On the basis of this model, the clearance capacity increased from birth to 5 years by a factor of 4.5 because of maturation. Maturation progressed exponentially, with a half-life of 14 months. This model was used to develop dosing regimen guidelines for pediatric patients aged 3.5 months and older.