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JAC Advance Access originally published online on March 19, 2009
Journal of Antimicrobial Chemotherapy 2009 63(5):1043-1049; doi:10.1093/jac/dkp073
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© The Author 2009. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Original research

Eight years' experience of an extended-interval dosing protocol for gentamicin in neonates

Evan J. Begg1,*, Jane W. A. Vella-Brincat1, Barbara Robertshawe2, Mark J. McMurtrie3, Carl M. J. Kirkpatrick3 and Brian Darlow4

1 Department of Clinical Pharmacology, Christchurch Hospital, Christchurch, New Zealand 2 Pharmacy Department, Christchurch Hospital, Christchurch, New Zealand 3 School of Pharmacy, The University of Queensland, Brisbane, Australia 4 Neonatal Intensive Care Unit, Christchurch Women's Hospital, Christchurch, New Zealand

Received 17 December 2008; returned 5 January 2009; revised 11 February 2009; accepted 13 February 2009

* Corresponding author. Tel: +64-3-364-1055; Fax: +64-3-364-1003; E-mail: evan.begg{at}otago.ac.nz

Background: Dosing of gentamicin in neonates in Christchurch has been carried out since 2000 using a locally developed extended-interval dosing protocol. All dosing data have been recorded in a database.

Aims: The aims of this study were to analyse the database to determine what percentage of neonates achieved target values for Cmax, Cmin and AUC, and to use the pharmacokinetic values of gentamicin to simulate new dosing protocols.

Methods: Cmax, Cmin and AUC were compared with target values. Clearance (CL), volume of distribution (V) and half-life (t1/2) were estimated, and used to produce new predictive dosing protocols that were tested and compared with the results of the original protocol.

Results: Gentamicin concentrations from 1461 individual doses were recorded in the database. Four hundred and eight were excluded. Of the remaining 1053, 84% achieved the target Cmax (>10 mg/L), 77% the target Cmin (<1 mg/L) and 63% the target AUC (within 80% to 125%). The number achieving target Cmax and Cmin values was improved markedly by prolonging the dosing intervals, but not by altering the predictive equations. Since the majority of the neonates only received a single dose of gentamicin, a new V-based model was also tested, and performed well. CL (L/kg) increased, while V (L/kg) and t1/2 (h) both decreased with respect to weight.

Conclusions: Extending the dose interval improved the success in achieving target Cmax and Cmin, while revision of the dosing equation did not. A V-based model provides an alternative approach to the first dose of gentamicin in neonates.

Keywords: aminoglycosides , pharmacokinetics , therapeutic drug monitoring


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