Re: How to include a dynamic covariate
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
Quoted reply history
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
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