Re: GAM analysis and further action

From: "Manish Gupta" guptam@email.chop.edu Subject: Re: [NMusers] GAM analysis and further action Date: Wed, 29 Mar 2006 14:06:39 -0500 Toufigh, I think you need to use an allometric model to describe between subject differences in CL and V. CL and V in the pediatric population most likely varies due to differences in body weight. If it is hepatically cleared drug, an allometric exponent of 0.75 is used for CL and an allometric exponent of 1 to be used for Volume of distribution. TVCL~CL*(BW/BWmedian)**0.75 TV~V*(BW/BWmedian)**1 For renally, cleared drugs, an exponent of 0.67 is used for CL. Once you have included Clearance and Volume as a function of body weight in your base model, you can look at the influence of other covariates like Hb in your analysis. As Mats pointed out, since HT and BW are highly correlated covariates, you can only include one of them in your GAM analysis (most likely BW). GAM analysis (in X-pose) does not account for correlated covariates since univariate analyses are performed. Some useful references discussing it 1. Anderson BJ, McKee D, Holford NHG. Size, myths and the clinical pharmacokinetics of analgesia in paediatric patients. Clinical Pharmacokinetics 1997;33:313-327 2. 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 3. Holford NHG. A size standard for pharmacokinetics. Clinical Pharmacokinetics 1996;30:329-332 I hope this was helpful Manish Manish Gupta, PhD Post Doctoral fellow Clinical Pharmacology & Therapeutics The Children's Hospital of Philadelphia Manish Gupta, PhD Post Doctoral fellow Clinical Pharmacology & Therapeutics The Children's Hospital of Philadelphia