Re: Scaling of pharmacokinetics in peds

From: Nick Holford - n.holford@auckland.ac.nz Subject: Re: [NMusers] Scaling of pharmacokinetics in peds Date: 12/20/2003 7:36 PM Jenny, Thanks for the additional reference which I had not seen before. This is an excellent source for experimental confirmation of allometric scaling, in particular an exponent of 0.75 for metabolic clearance. I was surprised, as were the authors, that an exponent closer to 0.67 was observed for renal clearance. This would be a good area for future allometric/physiological research to try to understand why this might be and why measures of renal functon (e.g. GFR) seem to scale with an exponent of 0.75. You bring up a good point about age and Km. I agree with you that any such relationship can only be considered empirical and does not have any theoretical backing like allometric scaling can provide. I mentioned age and Km as an example because it is one of the results from a very early population analysis of the pharmacokinetics of phenytoin by Ted Grasela et al. I am not sure of the reference. I think it was in JPB but cannot locate it via PubMed. I think of Km as an enzyme molecule property and would not expect this to change by simply increasing the number of molecules as body mass increases. Estimates of Km in vivo are more complex and hard to estimate. I expect they could be 'contaminated' by size if blood flow is an important determinant of clearance. 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/