Hi Abdullah Sultan, Since your estimate is not too far from 0.75 exponent in Clearances, did you try using the theoretical allometric scaling (0.75 in all clearances and 1.00 in volumes)? With these, it would be easier to justify. Once you include the body size, I would suggest you check the matrix plots of ETA in CL or V versus other covariates (demo, labs, etc) to see if there is any other info would help explain the variability. Without knowing more of the nature of the drug, I think these would help build the model.
Hope this helps, Rudy From: [email protected] [mailto:[email protected]] On Behalf Of Sultan,Abdullah S Sent: Tuesday, December 08, 2015 4:40 PM To: [email protected] Subject: [NMusers] Weight based dosing Hi everyone, I am developing a POP PK model for an anti-infective drug, I am trying to determine if dosing should be weight based or not. The range of weight in the study was 40-100 kg. Weight was statistically significant for Cl/F but only explained 9% of the variability observed for Cl. I used allometric scaling to describe weights effect on Cl/F and slope effect of weight was 0.58, and scaled to 60 kg (the median). Based on the slope effect estimated, AUC is predicted to decrease by 15% for an 80 kg individual, and increase by 25% for an individual that weights 40 kg compared to a 60 kg individual. How much should I trust the slope effect determined by my study? and should I rely on it to develop the dosing regimen? if weight only explained 9% of variability observed with Cl/F, could that indicate that it is not clinically significant and weight based dosing is not required? Thanks, Abdullah Sultan, PhD candidate University of Florida
