Article Text

O-38 The influence of body composi-tion on paediatric drug dosing
  1. Al-Sallami
  1. University of Otago, DUNEDIN, New Zealand


Background Body size is an important patient covariate in scaling drug doses. While total body weight has been the most commonly used size descriptor, fat free mass (FFM) has been advocated as an alternative size descrip-tor to scale drug doses in adults and children. FFM de-scribes the non-fat component of the body thus having a better correlation with the metabolic rate and drug clear-ance (CL). The aim of this work was to evaluate FFM as a covariate in a PK model of unfractionated heparin (UFH) developed in a paediatric population.

Methods Data from 64 infants and children who re-ceived 75–100 IU/kg of UFH during cardiac angiography were analysed. Four plasma samples were collected at baseline and at 15, 30, 45, and 120 min post-dose. UFH concentration (231 measurements) was quantified using a protamine titration assay. UFH effect (164 mea-surements) was quantified using activated partial throm-boplastin time (aPTT). A PKPD model was fitted to the data using the non-linear mixed effects modelling (in NONMEM v7.2). Various patient covariates such as age, weight (Wt), body surface area, and FFM were tested. The final model was evaluated using the likelihood ratio test and visual predictive checks (VPCs).

Results A one-compartment model with linear elimina-tion provided the best fit for the dose-concentration data. Wt and FFM had substantial influence on model fit; FFM was preferred statistically. A linear model provided the best fit for the concentration-effect data using the PPP and D sequential estimation method. Censored PD data (above the upper limit of quantification) were accounted for us-ing likelihood estimation. The PKPD model performed well using visual predictive checks.

Conclusion A PKPD model to describe the time-course of UFH effect was developed in a paediatric population which received a high single bolus dose. FFM was shown to describe drug disposition well and can potentially be used in dose calculation after appropriate evaluation.

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