Influence of maturation and growth on cefetamet pivoxil pharmacokinetics: rational dosing for infants.
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.
Hayton
W L
WL
College of Pharmacy, Ohio State University, Columbus 43210-1291, USA.
Kneer
J
J
de Groot
R
R
Stoeckel
K
K
D000284:Administration, Oral; D000328:Adult; D000375:Aging / Q000378:metabolism*; D001682:Biological Availability; D001835:Body Weight / Q000502:physiology; D015296:Ceftizoxime / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D008297:Male; D013530:Surgical Wound Infection / Q000517:prevention & control
D015296:Ceftizoxime; C047445:cefetamet pivoxyl