Format

Send to

Choose Destination
Antimicrob Agents Chemother. 2018 Apr 26;62(5). pii: e02238-17. doi: 10.1128/AAC.02238-17. Print 2018 May.

Pharmacokinetics of Penicillin G in Preterm and Term Neonates.

Author information

1
Pediatric Intensive Care Unit, Tartu University Hospital, Tartu, Estonia.
2
UCL Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.
3
Paediatric Infectious Diseases Research Group, Institute for Infection and Immunity, St. George's University of London, London, United Kingdom.
4
Institute of Chemistry, University of Tartu, Tartu, Estonia.
5
Clinic of Haematology and Oncology, North Estonia Medical Centre, Tallinn, Estonia.
6
Institute of Computer Science, University of Tartu, Tartu, Estonia.
7
Department of Microbiology, University of Tartu, Tartu, Estonia hiie.soeorg@ut.ee.
8
Department of Microbiology, University of Tartu, Tartu, Estonia.

Abstract

Group B streptococci are common causative agents of early-onset neonatal sepsis (EOS). Pharmacokinetic (PK) data for penicillin G have been described for extremely preterm neonates but have been poorly described for late-preterm and term neonates. Thus, evidence-based dosing recommendations are lacking. We describe the PK of penicillin G in neonates with a gestational age (GA) of ≥32 weeks and a postnatal age of <72 h. Penicillin G was administered intravenously at a dose of 25,000 or 50,000 IU/kg of body weight every 12 h (q12h). At steady state, PK blood samples were collected prior to and at 5 min, 1 h, 3 h, 8 h, and 12 h after injection. Noncompartmental PK analysis was performed with WinNonlin software. With those data in combination with data from neonates with a GA of ≤28 weeks, we developed a population PK model using NONMEM software and performed probability of target attainment (PTA) simulations. In total, 16 neonates with a GA of ≥32 weeks were included in noncompartmental analysis. The median volume of distribution (V) was 0.50 liters/kg (interquartile range, 0.42 to 0.57 liters/kg), the median clearance (CL) was 0.21 liters/h (interquartile range, 0.16 to 0.29 liters/kg), and the median half-life was 3.6 h (interquartile range, 3.2 to 4.3 h). In the population PK analysis that included 35 neonates, a two-compartment model best described the data. The final parameter estimates were 10.3 liters/70 kg and 29.8 liters/70 kg for V of the central and peripheral compartments, respectively, and 13.2 liters/h/70 kg for CL. Considering the fraction of unbound penicillin G to be 40%, the PTA of an unbound drug concentration that exceeds the MIC for 40% of the dosing interval was >90% for MICs of ≤2 mg/liter with doses of 25,000 IU/kg q12h. In neonates, regardless of GA, the PK parameters of penicillin G were similar. The dose of 25,000 IU/kg q12h is suggested for treatment of group B streptococcal EOS diagnosed within the first 72 h of life. (This study was registered with the EU Clinical Trials Register under EudraCT number 2012-002836-97.).

KEYWORDS:

early-onset sepsis; group B streptococcus; late-preterm neonate; noncompartmental analysis; population pharmacokinetics; term neonate

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center