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Antimicrobial Agents and Chemotherapy, June 2007, p. 1995-2000, Vol. 51, No. 6
0066-4804/07/$08.00+0     doi:10.1128/AAC.01506-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Pharmacokinetics of Penicillin G in Very-Low-Birth-Weight Neonates{triangledown}

Tuuli Metsvaht,1* Kersti Oselin,2 Mari-Liis Ilmoja,3 Kaili Anier,4 and Irja Lutsar5

Pediatric and Neonatal Intensive Care Unit, Clinic of Anesthesiology and Intensive Care, Tartu University Clinics,1 Institute of Pharmacology, Tartu University,2 Pediatric and Neonatal Intensive Care Unit, Tallinn Children's Hospital,3 Institute of Pharmacology, Tartu University,4 Institute of Microbiology, Tartu University, Tartu, Estonia5

Received 29 November 2006/ Returned for modification 2 February 2007/ Accepted 10 March 2007

Data on the pharmacokinetics (PKs) of penicillin G (PEN) in neonates date back to the 1970s and do not include data for very-low-birth-weight (VLBW) neonates. The aim of this study was to describe the steady-state PKs and to establish an optimal regimen for the dosing of PEN in neonates with gestational ages of less than 28 weeks and birth weights of less than 1,200 g. Two PEN dosing regimens were studied: 50,000 IU (30 mg)/kg of body weight every 12 h (q12h) (group 1; n = 9) and 25,000 IU (15 mg)/kg q12h (group 2; n = 9). Samples for PK analysis were drawn before the injection of PEN and at 2 and 30 min and 1.5, 4, 8, and 12 h after intravenous injection of the third to eighth PEN doses. The PEN concentration was measured by a high-performance liquid chromatography with UV detection technique. The median peak and trough concentrations of PEN were 147 µg/ml (lower and upper quartiles, 109 and 157 µg/ml, respectively) and 7 µg/ml (lower and upper quartiles, 5 and 13 µg/ml, respectively) after administration of the dose of 50,000 IU and 59 µg/ml (lower and upper quartiles, 53 and 78 µg/ml, respectively) and 3 µg/ml (lower and upper quartiles, 3 and 4 µg/ml, respectively) after administration of the dose of 25,000 IU. The PEN half-life (median and lower and upper quartiles for group 1, 3.9 h and 3.3 and 7.0 h, respectively; median and lower and upper quartiles for group 2, 4.6 h and 3.8 and 5.6 h, respectively) was longer in VLBW neonates than in adults and term infants. PEN renal clearance correlated with creatinine clearance (R2 = 0.309596; P = 0.038). Only a median of 34% (lower and upper quartiles, 28 and 37%, respectively) of the administered dose was excreted in urine within the following 12 h. We conclude that in VLBW infants a PEN dose of 25,000 IU (15 mg)/kg q12h is safe and sufficient to achieve serum concentrations above the MIC90 for group B streptococci for the entire dosing interval.

* Corresponding author. Mailing address: Neonatal Intensive Care Unit, Tartu University Clinics, Lunini 6, 51014 Tartu, Estonia. Phone: 372 7319 550. Fax: 372 7319 503. E-mail: tuuli.metsvaht{at}kliinikum.ee

{triangledown} Published ahead of print on 19 March 2007.

Antimicrobial Agents and Chemotherapy, June 2007, p. 1995-2000, Vol. 51, No. 6
0066-4804/07/$08.00+0     doi:10.1128/AAC.01506-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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