Re: Inclusion of covariates and model improvement

From: Nick Holford n.holford@auckland.ac.nz Subject: Re: [NMusers] Inclusion of covariates and model improvement Date: Thu, 20 Oct 2005 18:03:18 +1300 Toufigh, The model proposed by Leonid is an empirical allometric model. However, there is a substantial amount of theory and evidence to believe that the allometric exponent is 1 for volume and 0.75 for clearance. I would recommend using theory rather than empiricism if you intend to use your model for prediction or simulation (extrapolation). A more coherent approach would be to apply allometric scaling to all PK parameters that are known to vary with size e.g. CL, Q, V1, V2. I can think of no sensible reason to believe that these parameters should be modelled as if they did not vary with size. Centering of the parameter e.g. on a weight of 70 kg is always a good idea. Primarily because it means that the population parameter estimate refers to a general individual of standard and clearly specified size (or age or Clcr etc). There may also be some statistical advantages in producing more robust parameter estimates (lower imprecision) but this is not very sensitive in my experience to any plausible value e.g. there is no appreciable difference in the predictions if one centers on 70kg or on 10 kg when doing analyses of children with a median weight around 10 kg. Nick -- Nick Holford, Dept Pharmacology & Clinical Pharmacology University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand email:n.holford@auckland.ac.nz tel:+64(9)373-7599x86730 fax:373-7556 http://www.health.auckland.ac.nz/pharmacology/staff/nholford/