RE: How to include a dynamic covariate
The simplest approach is using a standard, nonlinear model for clearance (e.g.,
Michaelis-Menten). However, from your apparent interest in parameters like
cardiac output (CO?) and mean arterial blood pressure (MABP?) I gather that
this drug may change blood flow to the clearance organ. As such, a
semi-physiological, organ clearance model that incorporates a pharmacodynamic
effect on blood flow seems appropriate.
Your own search for references would certainly benefit from the details that
you alone possess. However, a good overview and comprehensive list of
references that cover clearance concepts, physiological models, and some
pharmacodynamics can be found in the following commentary.
Br J Clin Pharmacol. 2005 December; 60(6): 581-583.
Physiologically based pharmacokinetic modelling: a sound mechanistic basis is
needed
L Aarons
Regards,
Jeff Wald
Quoted reply history
From: [email protected] [mailto:[email protected]] On
Behalf Of Olinto Linares
Sent: Thursday, September 09, 2010 2:49 PM
To: [email protected]
Cc: [email protected]; Olinto Linares-Perdomo
Subject: [NMusers] How to include a dynamic covariate
Dears
We have been working in a pk model to prove that a drug can changes its own
kinetics as a function of dose. Standards pharmacokinetics models assume a
linear relationship between dose and plasma concentrations.Till now our results
show clearly a non-linearity between dose and drug-kinetics, using dose as
covariate. But we are interested to include a dynamic covariate like CO, CI
and/or MABP as covariate using differential equation solutions .
Any suggestions, reference papers, ideas
Thanks so much
Olinto
Olinto-Jose Linares-Perdomo, BS in Electrical Engineering, M.S., Ph.D.
Biomedical Informatics Department & Pharmaceutics Department.
University of Utah-USA
Office:(801)-585-5287
Cell: 001-(801)-783-9487
Fax: (801)-581-3467
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