Population pharmacokinetics of ceftizoxime in premature newborns.
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.
Karna
P
P
Michigan State University, East Lansing.
Lee
C
C
Kumar
A
A
Dyke
J
J
Gooch
W M
WM
D015296:Ceftizoxime / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000378:metabolism*; D008297:Male; D008954:Models, Biological
D015296:Ceftizoxime