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Dear Colleagues:
We are planning to conduct a food effect study. I wanted to know the
ideal washout duration between the two crossover periods (fed and
fasting states)? The FDA guidelines on food-effect studies does not
mention the duration of washout. The half-life of the compound is
between 6-8 hours and the PK is linear. Based on the half-life, is a
5-7 day washout sufficient? Any experiences posted will be greatly
appreciated.
A Barve, M.D, Ph.D.
Assistant Medical Director
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[Two replies - db]
Date: Sat, 19 Feb 2000 00:07:51 -0700 (MST)
X-Sender: ml11439.-at-.pop.goodnet.com
To: PharmPK.-at-.boomer.org
From: ml11439.-at-.goodnet.com (Michael J. Leibold)
Subject: Re: PharmPK Food effect study: Washout period
Dr.Barve,
A pharmacokinetic model which may provide some insight would
be that of the aminoglycosides, whose tissue distribution properties
result in a washout phase with a half-life of around 100 hours. This
would indicate that unless there is tissue binding third phase in
the drug's pharmacokinetics, a washout period of 5-7 days would be
sufficient for a drug with a "terminal" T1/2 of 6-8 hours. However,
another caveat could be diazepam which has an active metabolite with
a longer half-life than the parent drug (desmethyldiazepam with a
half-life of 60 hours versus 24-48 hours for diazepam). Another
possible problem would variance in the half-life due to factors
such as age, obesity, protein binding, heaptic/renal function etc.
Mike Leibold, PharmD, RPh
ML11439.at.goodnet.com
---
From: ksbae.at.snu.ac.kr
To:
Subject: Re: PharmPK Food effect study: Washout period
Date: Sun, 20 Feb 2000 15:16:55 +0900
X-Priority: 3
Dear All,
Usually 1 week of washout period is sufficient in your case
(Terminal half life 6-8 hours).
Sometimes it is not adequate.
Some kinds of drug can affect the PK(Absorption, Distribution,
Metabolism, Excretion) of second period.
Especially if the drug make somewhat long standing effect.
For example, when there occurs p-glycoprotein induction, there might
be period effect.
I saw two cases of period effect with cyclosporine when the washout
period is 1 week.
But with 2 weeks of washout period, there was no problem like that.
I think cytotoxic drug might induce p-glycoprotein in intestinal
epithelial membrane.
Consequently this can reduce the amount of absorption at the second period.
In my humble opinion, at least two weeks of washout period is
preferred for drugs like cyclosporine.
Kyun-Seop Bae M.D.
Clinical Pharmacology Unit
Seoul National University Hospital
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Dear Dr. Barve,
Yes, 5-7 days is more than adequate. In principle, > 99% i.v. of administered
dose is eliminated in 7 half-lives.
Sri Melethil, Ph.D.
Professor of Pharmaceutics and Medicine
University of Missouri-KC
School of Pharmacy
Room 203-B, 5005 Rockhilll Road
Kansas City, MO 64110
816-235-1794 (fax: 816-235-5190)
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