Population pharmacokinetics of amphotericin B in children with malignant diseases: Population pharmacokinetics of amphotericin B (original) (raw)
2002, British Journal of Clinical Pharmacology
Aims To construct a population pharmacokinetic model for the antifungal agent, amphotericin B (AmB), in children with malignant diseases. Methods A two compartment population pharmacokinetic model for AmB was developed using concentration-time data from 57 children aged between 9 months and 16 years who had received 1 mg kg x1 day x1 doses in either dextrose (doseform=1) or lipid emulsion (doseform=2). P-Pharm (version 1.5) was used to estimate the basic population parameters, to identify covariates with signi®cant relationships with the pharmacokinetic parameters and to construct a Covariate model. The predictive performance of the Covariate model was assessed in an independent group of 26 children (the validation group). Results The Covariate model had population mean estimates for clearance (CL), volume of distribution into the central compartment (V ) and the distributional rate constants (k 12 and k 21 ) of 0.88 l h x1 , 9.97 l, 0.27 h x1 and 0.16 h x1 , respectively, and the intersubject variability of these parameters was 19%, 49%, 55% and 48%, respectively. The following covariate relationships were identi®ed: CL (l h x1 )=0.053+0.0456 weight 0.75 (kg)+0.242 doseform and V (l)=7.11+0.107 weight (kg). Our Covariate model provided unbiased and precise predictions of AmB concentrations in the validation group of children: the mean prediction error was 0.0089 mg l x1 (95% con®dence interval: x0.0075, 0.0252 mg l x1 ) and the root mean square prediction error was 0.1245 mg l x1 (95% con®dence interval: 0.1131, 0.1349 mg l x1 ). Conclusions A valid population pharmacokinetic model for AmB has been developed and may now be used in conjunction with AmB toxicity and ef®cacy data to develop dosing guidelines for safe and effective AmB therapy in children with malignancy.
Loading Preview
Sorry, preview is currently unavailable. You can download the paper by clicking the button above.