INFLUENCE OF MATURATION AND GROWTH ON CEFETAMET PIVOXIL PHARMACOKINETICS, RATIONAL DOSING FOR INFANTS

The pharmacokinetics of intravenous (i.v.) cefetamet and the bioavaila bility of oral cefetamet pivoxil in infants aged 3.5 to 17.3 months wh o were hospitalized for urological surgery were characterized, The abs orption of cefetamet pivoxil administered in a syrup formulation was 3 8 +/- 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, T his was not different from the value observed for normal adult subject s but was longer than that reported for children aged 3 to 12 years, U rinary 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 wa s 399 +/- 116 ml/kg of body weight. It was comparable in size and show ed the same dependence on body weight as it did in children and adults , The mean systemic clearance per kilogram of body weight in the infan ts was lower than that in children and adults, apparently because of i mmaturity of clearance processes. A model that accounted for maturatio n and growth with increasing age was developed for the clearance, On t he basis of this model, the clearance capacity increased from birth to 5 years by a factor of 4.5 because of maturation, Maturation progress ed exponentially, with a half-life of 14 months, This model was used t o develop dosing regimen guidelines for pediatric patients aged 3.5 mo nths and older.