Back to the Top
Dear Mr. Virendra Patel,
Please note that washout period determination criteria are not only
governed by half life of a compound. An example of a Pharmacokinetic
Model of amino glycoside, tissue distribution results in a washout
period of 100hours.For example digoxin (a P-gp substrate) resulted
in interpatient variability observed in the pharmacokinetics.
Moreover drug half life period may be shorter than its metabolite.
Let's take the example of diazepam which has an active metabolite
with a longer half-life than the parent drug -desmethyl diazepam with
a half-life of 60 hours versus 24-48 hours for diazepam. In your case
an extended period from 7days is given which might be compound
specific effect of the drug because there are cases where drug can
affect the PK(Absorption, Distribution,Metabolism, Excretion) of
second period. More precisely when there is glycoprotein induction
(cytotoxic drug can induce p-glycoprotein in intestinal epithelial
membrane) there might be period effect. For example drug like
cyclosporine wash out period of 7days gave a period effect. But with
2weeks of washout period effect was eliminated.Same is the case for
veramapil which is P-gp inhibitor.
My humble opinion also suggests you to look for possible problem
related to variance in the half-life due to factors such as age,
obesity, protein binding, hepatic/renal function etc and
pharmacodynamic property of the drug.
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 "Washout period in BA/BE study" as the subject
Support PharmPK by using the
Copyright 1995-2011 David W. A. Bourne (email@example.com)