This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Muller, A. E.
Right arrow Articles by van den Anker, J. N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Muller, A. E.
Right arrow Articles by van den Anker, J. N.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, October 2007, p. 3720-3725, Vol. 51, No. 10
0066-4804/07/$08.00+0     doi:10.1128/AAC.00318-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Pharmacokinetics of Penicillin G in Infants with a Gestational Age of Less than 32 Weeks{triangledown}

Anouk E. Muller,1* Joost DeJongh,2,3 Ymka Bult,4,{dagger} Wil H. F. Goessens,5 Johan W. Mouton,6 Meindert Danhof,2,3 and John N. van den Anker4,7

Medical Centre Haaglanden, Department of Obstetrics and Gynecology, Lijnbaan 32, 2512 VA The Hague, The Netherlands,1 LAP&P Consultants BV, Archimedesweg 31, 2333 CM Leiden, The Netherlands,2 Leiden-Amsterdam Center for Drug Research, Leiden University, Division of Pharmacology, P.O. Box 9502, 2300 RA Leiden, The Netherlands,3 Erasmus MC-Sophia, Sophia Children's Hospital, Dr Molewaterplein 60, 3015 GJ Rotterdam, The Netherlands,4 Erasmus MC, University Medical Centre Rotterdam, Department of Medical Microbiology, Dr Molewaterplein 60, 3015 GJ Rotterdam, The Netherlands,5 Canisius Wilhelmina Hospital, Department of Clinical Microbiology and Infectious Diseases, Nijmegen, The Netherlands,6 Children's National Medical Center, Division of Pediatric Clinical Pharmacology, 111 Michigan Avenue, N.W., Washington, DC 200107

Received 7 March 2007/ Returned for modification 10 June 2007/ Accepted 15 July 2007

The pharmacokinetics of penicillin G were studied in 20 preterm neonates with a gestational age of less than 32 weeks on day 3 of life by using a population approach performed with the nonlinear mixed effects modeling program NONMEM. The derived population estimates and the correlation matrix of these estimates were used to perform Monte Carlo simulations and obtain the probability of target attainment (PTA). The pharmacokinetics of penicillin G were best described by a two-compartment pharmacokinetic model. The population estimates of the central volume of distribution, the peripheral volume of distribution, the intercompartmental clearance, and the total body clearance were 0.359 ± 0.06 liter, 0.152 ± 0.03 liter, 0.774 ± 0.28 liter/h, and 0.103 ± 0.01 liter/h (mean ± standard error), respectively. The terminal half-life was 3.9 h. Clearance increased significantly with increasing birth weight. Assuming the percentage of time that the concentration of unbound drug remained above the MIC of 50% for preterm neonates, the susceptibility breakpoint based on a 100% PTA was ≤4 mg/liter, simulating the current dosing regimen of 50,000 U/kg every 12 h. This regimen is therefore adequate for the treatment of common infections in neonates on the third day of life.

* Corresponding author. Mailing address: Medical Centre Haaglanden (MCH), Department of Obstetrics and Gynecology, Lijnbaan 32, 2512 VA The Hague, The Netherlands. Phone: 31-70-3302000. Fax: 31-70-3302248. E-mail: a.muller{at}mchaaglanden.nl

{triangledown} Published ahead of print on 23 July 2007.

{dagger} Present address: Wilhelmina Hospital Assen, Department of Pediatrics, Europaweg-Zuid 1, 9401 RK Assen, The Netherlands.

Antimicrobial Agents and Chemotherapy, October 2007, p. 3720-3725, Vol. 51, No. 10
0066-4804/07/$08.00+0     doi:10.1128/AAC.00318-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»