Amoxicillin pharmacokinetics in (preterm) infants aged 10 to 52 days: effect of postnatal age.
The pharmacokinetic parameters of amoxicillin were determined in 32 newborn infants aged 10 to 52 days (mean postnatal age, 24.7 +/- 12.4 days) to improve amoxicillin dosing in this age group. Amoxicillin plasma concentrations were determined using reversed-phase high-performance liquid chromatography in surplus plasma samples from routine gentamicin assays. Amoxicillin pharmacokinetic parameters (mean +/- SD) were as follows: first-order elimination constant (K(el)) = 0.27 +/- 0.10 h(-1), volume of distribution corrected for body weight (V/W) = 0.66 +/- 0.27 L/kg, total body clearance corrected for body weight (CL/W) = 0.18 +/- 0.10 Lkg(-1)h(-1), and elimination half-life (t(1/2)) = 3.0 +/- 1.3 hours. Amoxicillin body clearance was approximately twofold greater in our patients compared with published values in younger neonates (mean postnatal age, 0.76 +/- 1.57 days). Simulation studies using the observed amoxicillin pharmacokinetic data suggest an amoxicillin dose of 40 mg/kg administered every 8 hours in infants older than 9 days postnatal age, independent of gestational age and postconceptional age, to achieve satisfactory target plasma amoxicillin concentrations less than 140 mg/L and time above minimum inhibitory concentration of at least 40%. Prospective evaluation of this suggested new dosage regimen is necessary before implementation in the care of ill neonates.
Pullen
J
J
Department of Clinical Pharmacy and Toxicology, University Hospital of Maastricht, Maastricht, The Netherlands. jpul@kfls.azm.nl
Driessen
M
M
Stolk
L M L
LM
Degraeuwe
P L J
PL
van Tiel
F H
FH
Neef
C
C
Zimmermann
L J I
LJ
D000375:Aging / Q000378:metabolism; D000658:Amoxicillin / Q000097:blood / Q000493:pharmacokinetics*; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics*; D001835:Body Weight; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature; D007363:Intensive Care Units, Neonatal; D008297:Male; D008657:Metabolic Clearance Rate
D000900:Anti-Bacterial Agents; D000658:Amoxicillin