RE: Weight based dosing
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
Quoted reply history
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