[NMusers] PD modeling question

Hi Everyone,

I am trying to model the PK/PD relationships for three drugs that inhibit the uptake of a neurotransmitter using indirect response models with inhibition of output. The three drugs differ significantly in the rates by which they elevate the neurotransmitter and the rates at which the levels return back to the baseline. This result in significant differences in the model estimates of Kin and Kout for the three drugs despite the fact that the values of the baseline transmitter levels and consequently the Kin/Kout ratios are equal for the three drugs.

 The three drugs are known to interact with the same transporter even though there are suggestions of differences in the mechanism of that interaction.

Is the difference in the Kin among the drugs justified by the difference in the rate of elevation of the neurotransmitter? or is it contradictory to the theoretical basis of the model which defines Kin as the rate constant for production of response (or the neurotransmitter here) and consequently it should be equal for the three drugs?

Insights from the group and examples from the literature will be highly appreciated.

Thanks

Ahmed

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Ahmed Abdel-Fattah Othman
Ph.D. Candidate
Pharmacokinetics and Biopharmaceutics lab
School of Pharmacy
University of Maryland at Baltimore
20 Penn Street,HSF-2
Baltimore, MD 21201
Phone:(410)706-7388
E-Mail:- aothm001_at_umaryland.edu
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Received on Tue Jan 23 2007 - 14:38:51 EST