Hello Olinto,
Here are examples of physiologically based models that included drug
induced changes in blood flow and hence the drug influences its own
kinetics:
1. Upton RN, Ludbrook GL. Pharmacokinetic-pharmacodynamic modelling of
the cardiovascular effects of drugs - method development and application
to magnesium in sheep. BMC Pharmacology 2005; 5: 5-
2. Upton RN, Ludbrook GL. A physiologically based, recirculatory model
of the kinetics and dynamics of propofol in man. Anesthesiology 2005;
103: 344-52
Regards, Richard
Richard Upton
On 11/09/2010 2:55 AM, Jeff Wald wrote:
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
*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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