Re: Weight normailized doses in modeling

From: Nick Holford <n.holford@auckland.ac.nz> Subject: Re: [NMusers] Weight normailized doses in modeling Date: Mon, 29 Oct 2001 19:23:37 +1300 Thomas, The key issue here is what is "normal" about weight normalised units? Tradition (but not necessarily reason) has decided that doses/kg are "normal". But the relationship between key pharmacokinetic parameters such as clearance and half-life is not linearly related to weight. My advice is to use the actual dose and scale the model parameters using allometric science rather than flat earth tradition. See these references for the theory and application: Anderson BJ, Holford NHG. Aspects of theophylline clearance in children. Anaesth Intens Care 1997;25:497-501. Anderson BJ, McKee D, Holford NHG. Size, myths and the clinical pharmacokinetics of analgesia in paediatric patients. Clinical Pharmacokinetics 1997;33:313-327. Anderson BJ, Woolard G, Holford NHG. A model for size and age changes in the pharmacokinetics of paracetamol in neonates, infants and children. Br J Clin Pharmacol 2000;50:125-134. West GB, Brown JH, Enquist BJ. A general model for the origin of allometric scaling laws in biology. Science 1997;276:122-26. West GB, Brown JH, Enquist BJ. The fourth dimension of life: fractal geometry and allometric scaling of organisms. Science 1999;284(5420):1677-9. Nick -- Nick Holford, Divn Pharmacology & Clinical Pharmacology University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand email:n.holford@auckland.ac.nz tel:+64(9)373-7599x6730 fax:373-7556 http://www.phm.auckland.ac.nz/Staff/NHolford/nholford.htm