Re: Scaling of pharmacokinetics in peds

From: Jenny Yuehling Chien - CHIEN_JENNY_YUEHLING@lilly.com Subject: Re: [NMusers] Scaling of pharmacokinetics in peds Date: 12/19/2003 10:27 AM Nick and Pete, another good reference to support 0.75 for clearance: Hu and Hayton, Allometric scaling of xenobiotic clearance: uncertainty vs universality. AAPS PharmSci 2001; 3(4) article 29. The treatment of Km will depend on the source of nonlinearity. If source of nonlinearity is metabolism-based, tons of literature exist on ontogeny of drug metabolizing enzymes to support no scaling on Km, I would agree the effect of weight would only be on Vmax. If source of nonlinearity is due to other biological factors, you will need to know the impact of age-related physiological changes on the empirical "Km," in that case, I imagine simple scaling on Km would not make any sense either. Jenny Chien, PhD research scientist Global PK/PD & TS Lilly Research Laboratories Lilly Corporate Center Indianapolis, IN 46285