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RE: Population PKPD using hair drug concentration

From: Krzyzanski, Wojciech <wk>
Date: Fri, 12 Jun 2015 14:59:49 +0000

Dear Bernard,
If you observed a long delay between your measurement and exposure to plasma drug concentration and you do not want to model the mechanisms underlying delay, the simples way to start is to use the delayed plasma concentration C(t-Tdel). For example, the Emax model with delay will be
E(t)=Emax*C(t-Tdel)/(EC50+C(t-Tdel)), etc. You can implement Tdel in NONMEM using the ALAG feature.
What Leonid suggests might work, but then you need to interpret the transit compartments and you will need a lot of them. The link model (effect compartment) makes sense, but might not work if the delay is too long.
My gut feeling is that to model drug concentration in hair you will need more complex models handling delays than any of these.

-----Original Message-----
From: owner-nmusers] On Behalf Of Leonid Gibiansky
Sent: Friday, June 12, 2015 9:55 AM
To: Bernard Ngara;
Subject: Re: [NMusers] Population PKPD using hair drug concentration

Dear Bernard,

This looks like really interesting problem. Based on the idea that it should be a long delay, I would start with the transit compartment model (you can google for the references on this type of models) with the input from the plasma compartment. The last compartment will represent a barber shop. The number of transit compartment can be increased until you get a sufficiently long delay. Observation compartment can be either the last one, or the sum of several, depending on how measurements are done (at a particular hair length, or by grinding the hair together before measurement). Depending on whether hair can eliminate the drug (or it happens only in the barber shop), hair clearance can be assigned to all or only to the last of those transit compartments.

It could be that a simple effect compartment model with a very slow ke0 could describe it as well but you should be able to see it by increasing or decreasing the number of transit compartments.


Leonid Gibiansky, Ph.D.
President, QuantPharm LLC
e-mail: LGibiansky at
tel: (301) 767 5566

On 6/12/2015 8:56 AM, Bernard Ngara wrote:
> Dear all
> I am a working on a study that measures both short and long term
> exposure to drug using plasma and hair drug concentration. What
> methods can I use to model hair drug concentration. You can give
> references so that I can read.
> Thanks once again.
> Regards
Received on Fri Jun 12 2015 - 10:59:49 EDT

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