Relationship between clinical and biologic variables and chloramphenicol pharmacokinetic parameters in pediatric patients with sepsis

OBJECTIVE: To evaluate the influence of several clinical and biologic factors on the disposition kinetics of oral chloramphenicol in pediatric patients and to determine the usefulness of this information to predict chloramphenicol serum concentrations. STUDY DESIGN: The clinical, biologic, and pharmacokinetic data of 30 consecutive pediatric patients diagnosed with sepsis and admitted to a tertiary care center were analyzed retrospectively. The patients were randomly assigned to a study group and a validation group. The model was developed by a three-step approach involving Bayesian estimation of pharmacokinetic parameters, selection of covariates by principal component analysis, and final selection by stepwise multiple linear regression. The model was tested in the study group and compared with a general population model using a prediction error analysis. RESULTS: Regression analysis revealed that weight, albumin, and white blood cell (WBC) count were the most important determinants for chloramphenicol distribution volume, whereas age, WBC count, and serum creatinine were the most important determinants for chloramphenicol clearance. The performance of the constructed population model improved significantly in terms of both bias and precision compared with the general model when tested in the validation group. CONCLUSIONS: Clinical and biologic factors may significantly influence chloramphenicol's disposition in pediatric patients with sepsis and therefore should be considered in programming dosage regimens.