A population approach to the forecasting of amikacin plasma and urinary levels using a prescribed dosage regimen

We retrospectively analyzed amikacin pharmacokinetics in 19 critically ill patients who received amikacin intravenously. Fourteen subjects (577 serum amikacin concentrations, 167 urine measurements) were studied to obtain data for population modeling, while 5 patients (267 serum amikacin concentrati...

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Bibliographic Details
Published in:European journal of drug metabolism and pharmacokinetics 1999-01, Vol.24 (1), p.39-46
Main Authors: Joubert, P, Bressolle, F, Gouby, A, Douçot, P Y, Saissi, G, Gomeni, R
Format: Article
Language:English
Subjects:
Amikacin - administration & dosage
Amikacin - blood
Amikacin - urine
Bayes Theorem
Creatinine
Female
Fluorescence Polarization Immunoassay
Humans
Injections, Intravenous
Kidney Function Tests
Male
Middle Aged
Retrospective Studies
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Summary:We retrospectively analyzed amikacin pharmacokinetics in 19 critically ill patients who received amikacin intravenously. Fourteen subjects (577 serum amikacin concentrations, 167 urine measurements) were studied to obtain data for population modeling, while 5 patients (267 serum amikacin concentrations, 68 urine measurements) were studied for the assessment of predictive performance. The population analysis was performed using serum and urine amikacin measurements; the renal clearance of amikacin was expressed as a function of creatinine clearance. A two-compartment model was fitted to the population data by using NONMEM. The population characteristics of the pharmacokinetic parameters (fixed and random effects) were estimated using the FOCE method. The population pharmacokinetic parameters with the interindividual variability (CV%) were as follows: slope (0.254, 126%) and intercept (3 l/h, 59.6%) of the linear model which relate the amikacin renal clearance to the creatinine clearance, initial volume of distribution (17.1 l, 22.2%), intercompartment clearance (5.22 l/h, 104%), steady state volume of distribution (55.2 l, 64.1%) and urinary elimination (67.5%, 36.3%). The Bayesian approach developed in this study accurately predicts amikacin concentrations in serum and urine and allows for the estimation of amikacin pharmacokinetic parameters, minimizing the risk of bias in the prediction.
ISSN:0378-7966
2107-0180
DOI:10.1007/BF03190009