PharmPK Discussion - PK/PD modeling of fast acting drugs

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On 3 Jun 2004 at 13:27:44, "Gordi, Toufigh" (Toufigh.Gordi.-at-.cvt.com) sent the message

Hello everyone,
I am in the process of modeling a compound which has a very fast onset
of the effect. The compound is administered iv in the left hand vein
and plasma samples for drug concentrations are collected at the right
hand vein. Before reaching the right hand vein, however, effects on
heart can be detected. This means that maximum effect is observed
before maximum plasma concentrations (which is observed 1-2 minutes
after administration). It takes 3-5 minutes for the drug to be evenly
distributed in the blood.
I would be grateful for references to PK/PD models dealing with similar
issues.
Best regards,
Toufigh Gordi

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On 4 Jun 2004 at 10:40:04, Nick Holford (n.holford.-a-.auckland.ac.nz) sent the message

Gordi,
I think Davide Verotta and Lewis Sheiner looked at some nicotine/heart
rate data (from Neil Benowitz) in which they modelled this kind of
situation where the sampled compartment (venous blood) is downstream
from the compartment driving the effects (arterial blood).
This might be a reference:
Verotta D, Sheiner LB. A general conceptual model for non-steady state
pharmacokinetic/pharmacodynamic data. J Pharmacokinet Biopharm
1995;23(1):1-4.
Nick
--
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New
Zealand
email:n.holford.at.auckland.ac.nz tel:+64(9)373-7599x86730 fax:373-7556
http://www.health.auckland.ac.nz/pharmacology/staff/nholford/

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