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Evaluating renal function and age as predictors of amikacin clearance in neonates: model‐based analysis and optimal dosing strategies
Author(s) -
Illamola Sílvia M.,
Colom Helena,
Hasselt J. G. Coen
Publication year - 2016
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.13016
Subject(s) - amikacin , dosing , medicine , pharmacokinetics , renal function , population , clearance , volume of distribution , creatinine , urology , nephrotoxicity , pharmacology , toxicity , chemistry , antibiotics , biochemistry , environmental health
Abstract Aims We aimed to compare the performance of renal function and age as predictors of inter‐individual variability (IIV) in clearance of amikacin in neonates through parallel development of population pharmacokinetic (PK) models and their associated impact on optimal dosing regimens. Methods Amikacin concentrations were retrospectively collected for 149 neonates receiving amikacin (post‐natal age (PNA) between 4–89 days). Two population PK models were developed in parallel, considering at least as predictors current body weight (WT), in combination with either creatinine clearance (CL cr ) or age descriptors. Using stochastic simulations for both renal function or age‐based dosing, we identified optimal dosing strategies that were based on attainment of optimal peak‐ (PCC) and trough target concentration coverage (TCC) windows associated with efficacy and toxicity. Results The CL cr and age‐based population PK models both included current body weight (WT) on CL, central distribution volume and intercompartmental clearance, in combination with either CL cr or PNA as predictors for IIV of clearance (CL). The WT‐CL cr model explained 6.9% more IIV in CL compared with the WT‐PNA model. Both models successfully described an external dataset ( n = 53) of amikacin PK. The simulation analysis of optimal dose regimens suggested similar performance of either CL cr or PNA based dosing. Conclusion CL cr predicted more IIV in CL, but did not translate into clinically relevant improvements of target concentrations. Our optimized dose regimens can be considered for further evaluation to optimize initial treatment with amikacin.