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

E. J. Begg, J. W. A. Vella-Brincat, B. Robertshawe, M. J. McMurtrie, C. M. J. Kirkpatrick, B. Darlow
2009 Journal of Antimicrobial Chemotherapy  
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 C max , C min and AUC, and to use the pharmacokinetic values of gentamicin to simulate new dosing protocols. Methods: C max , C min and AUC were compared with target values.
more » ... e (CL), volume of distribution (V) and half-life (t 1/2 ) 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 C max (>10 mg/L), 77% the target C min (<1 mg/L) and 63% the target AUC (within 80% to 125%). The number achieving target C max and C min 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 t 1/2 (h) both decreased with respect to weight. Conclusions: Extending the dose interval improved the success in achieving target C max and C min , while revision of the dosing equation did not. A V-based model provides an alternative approach to the first dose of gentamicin in neonates.
doi:10.1093/jac/dkp073 pmid:19299469 fatcat:eudhcn6ymjbrrpklmv25pfnbw4