RE: Population PKPD using hair drug concentration
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.
Regards,
Wojciech
Quoted reply history
-----Original Message-----
From: [email protected] [mailto:[email protected]] On
Behalf Of Leonid Gibiansky
Sent: Friday, June 12, 2015 9:55 AM
To: Bernard Ngara; [email protected]
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.
Regards,
Leonid
--------------------------------------
Leonid Gibiansky, Ph.D.
President, QuantPharm LLC
web: www.quantpharm.com
e-mail: LGibiansky at quantpharm.com
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
>