Previous Article | Next Article 
Antimicrobial Agents and Chemotherapy, April 2009, p. 1574-1580, Vol. 53, No. 4
0066-4804/09/$08.00+0 doi:10.1128/AAC.00119-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Pharmacokinetics of Amoxicillin in Maternal, Umbilical Cord, and Neonatal Sera
Anouk E. Muller,1*
Paul M. Oostvogel,2
Joost DeJongh,3,4
Johan W. Mouton,5
Eric A. P. Steegers,6
P. Joep Dörr,1
Meindert Danhof,3,4 and
Rob A. Voskuyl4
Medical Centre Haaglanden, Department of Obstetrics and Gynecology, Lijnbaan 32, The Hague 2512 VA, The Netherlands,1 Medical Centre Haaglanden, Department of Clinical Microbiology, Lijnbaan 32, The Hague 2512 VA, The Netherlands,2 LAP&P Consultants BV, Archimedesweg 31, Leiden 2333 CM, The Netherlands,3 Leiden-Amsterdam Center for Drug Research, Division of Pharmacology, Leiden University, P.O. Box 9502, Leiden 2300 RA, The Netherlands,4 Canisius Wilhelmina Hospital, Department of Clinical Microbiology and Infectious Diseases, Nijmegen, The Netherlands,5 Erasmus MC, University Medical Centre Rotterdam, Department of Obstetrics and Gynecology, Division of Obstetrics and Prenatal Medicine, 's-Gravendijkwal 230, Rotterdam 3015 CE, The Netherlands6
Received 27 January 2008/ Returned for modification 6 June 2008/ Accepted 8 January 2009
The pharmacokinetics of amoxicillin were studied in umbilical cord and neonatal sera relative to maternal concentrations in prevention of neonatal group B streptococcus infection. The subjects were 44 pregnant women receiving amoxicillin as 1 or 2 g as an intravenous infusion. To measure the concentrations, blood samples were obtained from the mother, the arterial and venous umbilical cord, and the neonate. The pharmacokinetics were characterized by a five-compartment model by using nonlinear mixed-effects (population) modeling. The population estimates for the clearance, central volume of distribution, and the two peripheral maternal volumes of distribution were 19.7 ± 0.99 liters/h, 6.40 ± 0.61 liters, and 5.88 ± 0.83 liters (mean ± standard error), respectively. The volume of distribution of the venous umbilical cord and the neonatal volume of distribution were 3.40 liters and 11.9 liters, respectively. The pharmacokinetic parameter estimates were used to simulate the concentration-time profiles in maternal, venous umbilical cord, and neonatal sera. The peak concentration in the venous umbilical cord serum was 18% of the maternal peak concentration. It was reached 3.3 min after the maternal peak concentration. The concentration-time profile in neonatal serum was determined by the profile in venous umbilical cord serum, which in turn depended on the profile in maternal serum. Furthermore, the simulated concentrations in maternal, venous umbilical cord, and neonatal sera exceeded the MIC for group B streptococcus for more than 90% of the 4-h dosing interval. In a first approximation, the 2-g infusion to the mother appears to be adequate for the prevention of group B streptococcal disease. However, to investigate the efficacy of the prophylaxis, further studies of the interindividual variability in pharmacokinetics are indicated.
* Corresponding author. Present address: Erasmus MC, University Medical Centre Rotterdam, Department of Clinical Microbiology and Infectious Diseases, 's-Gravendijkwal 230, Rotterdam 3015 CE, The Netherlands. Phone: 31-10-7033510. Fax: 31-10-7033075. E-mail: muller.research{at}gmail.com
Published ahead of print on 21 January 2009.
Antimicrobial Agents and Chemotherapy, April 2009, p. 1574-1580, Vol. 53, No. 4
0066-4804/09/$08.00+0 doi:10.1128/AAC.00119-08
Copyright © 2009, 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»