Amoxicillin pharmacokinetics in (Preterm) infants aged 10 to 52 days: Effect of postnatal age

• Published in: Therapeutic drug monitoring Vol. 29; no. 3; pp. 376 - 380
• Main Authors: PULLEN, J, DRIESSEN, M, STOLK, L. M. L, DEGRAEUWE, P. L. J, VAN TIEL, F. H, NEEF, C, ZIMMERMANN, L. J. I
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01-06-2007; Lippincott Williams & Wilkins Ovid Technologies
• Subjects: Aging - metabolism; Amoxicillin - blood; Amoxicillin - pharmacokinetics; Anti-Bacterial Agents - blood; Anti-Bacterial Agents - pharmacokinetics; Antibiotics; Babies; Biological and medical sciences; Body Weight; Chromatography; Drug Monitoring; Drug therapy; Female; Humans; Infant; Infant, Newborn; Infant, Premature; Intensive Care Units, Neonatal; Male; Medical sciences; Metabolic Clearance Rate; Neonatal care; Pharmacology; Pharmacology. Drug treatments; Side effects; Human; infants; β-Lactams; Infant; dosage regimen; Penicillin derivatives; Therapeutic drug monitoring; Antibiotic; Postnatal; Prematurity; Amoxicillin; postnatal age; Antibacterial agent; Pharmacokinetics; Age
• ISSN: 0163-4356; 1536-3694
• DOI: 10.1097/FTD.0b013e318067de5c

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.