Back to the Top
Hi everyone, how are you doing?
I heard that, in a two compartments model, in order to choose between the two t1/2(half-life times): t1/2alpha and t1/2beta , we must compare the [AUC]alpha=A/alpha and the [AUC]beta=B/beta..
For example if A/alpha > B/beta then we should choose t1/2(alpha)
Is that true ?
Back to the Top
The following message was posted to: PharmPK
Dear Yessin
I used to teach this in the past, as well as calculating a composite half-life from the fractional area of each phase multiplied by the respective half-lives.
But I now realize that this is incorrect and even for drugs with very long half-lives like diazepam and digoxin, where the terminal half-lives account for ~95% of the AUC, you will not correctly predict accumulation with this method. See our December 2008 paper, Sahin and Benet, Pharm. Res. 25:2869-2877, as well as my response to Nick Holford under the PharmPK heading Deciding the Dosing Interval on December 16.
Les
Leslie Z. Benet, Ph.D.
Professor
Department of Bioengineering & Therapeutic Sciences Schools of Pharmacy & Medicine
University of California San Francisco
533 Parnassus Avenue, Room U-68
San Francisco, CA 94143-0912
Back to the Top
The following message was posted to: PharmPK
Yessine Mechlia,
yessine mechlia wrote:
> I heard that, in a two compartments model, in order to choose between the two t1/2(half-life times): t1/2alpha and t1/2beta , we must compare the [AUC]alpha=A/alpha and the [AUC]beta=B/beta..
> For example if A/alpha > B/beta then we should choose t1/2(alpha)
> Is that true ?
>
I don't understand your question. Why do you want to choose between the two half-lives? A two compartment model has two half-lives - by convention the faster one is called lamda1 (alpha in an older terminology) and the slower is called lambdaz (beta). If you have a two compartment model then you have to have two half-lives -- you cannot choose to have only one.
Perhaps you are asking to decide which half-life is the most important in the sense of describing the total area under the curve. In that case you can calculate the fraction of AUC which is attributable to each half-life use the ratio of intercept to rate constant as you show below.
Nick
-- Nick Holford, Professor Clinical Pharmacology
Dept Pharmacology & Clinical Pharmacology
University of Auckland,85 Park Rd,Private Bag 92019,Auckland,New Zealand
Back to the Top
Dear Yessine
In two compartment model both alpha and beta half-live are important and not possible to ignore any one of these. compatrasion may help to evaluate the accumulation of drug in the body.
Dr Zafar
Want to post a follow-up message on this topic?
If this link does not work with your browser send a follow-up message to PharmPK@boomer.org with "Two compartment AUC" as the subject | Support PharmPK by using the |
Copyright 1995-2011 David W. A. Bourne (david@boomer.org)