Aims: Fat free mass (FFM) describes the non-fat component of the body. It has been advocated as an appropriate size descriptor to scale drug clearance (CL) and hence drug doses in adults and children. When compared to other size descriptors such as total body weight, FFM has been shown to correlate well with CL. Models for predicting FFM have been developed in adults but there is currently a paucity of mechanism-based models developed to predict FFM in children. The aim of this work was to develop and evaluate a model to predict FFM in children.
Methods: A large dataset (496 females and 515 males) was available for model building. Subjects had a relatively wide range of age (3 to 29 years) and body mass index values (12 to 44.9 kg/m2). Two types of models (M1 and M2) were developed to describe FFM in children. M1 was fully empirical and based on a linear model that contained all statistically significant covariates and their interactions. M2 was a simpler model that incorporated a maturation process. M1 was developed to provide the best possible description of the data (i.e. a positive control). In addition, a published adult model (M3) was applied directly as a reference description of the data (Janmahasatian et al, 2005). The predictive performances of the three models were assessed by visual predictive checks and by using mean error (ME) and root mean squared error (RMSE). A test dataset (90 females and 86 males) was available for external evaluation.
Results: M1 consisted of 9 terms with up to 2nd level interactions. M2 was a sigmoid hyperbolic model based on post-natal age with an asymptote at the adult prediction (M3). For the test data set, the ME and 95% CI for M1, M2 and, M3 were – 0.16 (- 0.32 to – 0.01), – 0.56 (- 0.87 to – 0.29) and – 1.49 (- 2.1 to – 0.91) kg, respectively and RMSE were 1.14 (0.98 to 1.33), 2.02 (1.5 to 2.49), and 4.32 (3.52 to 5.19) kg.
Conclusion: A maturation model that asymptoted to an established adult model was developed for prediction of FFM in children. This model was found to perform well in both male and female children. Interestingly, the adult model (M3) performed similarly to the maturation model to describe FFM in females. The ability to predict FFM in children from simple demographic measurements is expected to improve understanding of human body structure and function with an application in drug dosing.
References: 1. Janmahasatian et al. Quantificaiton of lean body weight. Clin Pharmacokinet 2005; 44(10): 1051-1065