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Dear all,
Does anybody know if is bioquivalence studies of antiretroviral
agents could be conduct in healthy volunteers?
Is ethical to do? Is it possible that this kind of protocol (single
dose in healthy volunteers) could be approval by Institutional Review Board?
Or is it better to conduct a bioequivalences multiples dose in HIV patients?
Could anybody advice me about it?
THank you
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BE studies for Anti-HIV drugs are routinely conducted in healthy
volunteers. These are usually single,dose crossover studies.
Vanitha Sekar,PhD
US FDA
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[A few more replies - db]
Sender: PharmPK.at.boomer.org
Reply-To: "Patrick Smith"
MIME-Version: 1.0
From: "Patrick Smith"
Date: Wed, 30 Aug 2000 15:53:11 -0400
To: david.aaa.boomer.org
Subject: Re: PharmPK Bioequivalence studies - healthy vs patient
The following message was posted to: PharmPK
The primary question is what type of antiretroviral are you looking to test?
For example, a protease inhibitor would be less concerning than a nucleoside
analogue. We have conducted several studies of antiretrovirals in healthy
volunteers, including nucleosides. They have all been single doses,
absolute bioavailability, food effects, and dose-ranging for
pharmacokinetics. There is a trend towards a more 'normal' course of
development for these drugs, which includes healthy volunteers. I am aware
of a number of compounds in pre-clinical development that are planning to go
into healthy volunteers initially. The risks of causing cancer in the
healthy volunteers after a single dose were felt to be small.....and it
should be pointed out that there are also important issues with conducting
1st time in man studies in HIV-infected patients. This could result in the
use of doses (or monotherapy regimens) that might be suboptimal, promoting
resistance, or might potentially interact with the large numbers of
additional drugs these patients are typically treated with. Therefore,
there are advantages and disadvantages of each approach, many questions and
few answers. A reference for a healhty volunteer study we did with a
nucleoside was recently published:
Smith PF, Forrest A, Ballow CH, Martin DE, Proulx L. Absolute
Bioavailability and Disposition of ( ) and (+) 2'-Deoxy-
3'-Oxa-4'-Thiocytidine (dOTC) following Single Intravenous and Oral Doses of
Racemic dOTC in Humans. Antimicrobial Agents and Chemotherapy,
2000;44:1609-1615.
Hope this helps,
Patrick Smith
Buffalo, NY
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Sender: PharmPK.at.boomer.org
Reply-To: "Eric Masson"
MIME-Version: 1.0
From: "Eric Masson"
Date: Wed, 30 Aug 2000 17:40:49 -0400
To: david.aaa.boomer.org
Subject: RE: PharmPK Bioequivalence studies - healthy vs patient
The following message was posted to: PharmPK
Most antiretroviral drugs can be tested in healthy volunteers as a single
dose.
Eric Masson, Pharm.D.
Scientific Director,
Anapharm inc
2050, boul Rene-Levesque West,
Ste-Foy, QC, Canada, G1V-2K8
Phone:418-527-4000 (EXT:5222)
FAX: 418-527-3456
emasson.aaa.anapharm.com
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Sender: PharmPK.-a-.boomer.org
Reply-To: gilberto de nucci
Mime-Version: 1.0
From: gilberto de nucci
Date: Wed, 30 Aug 2000 20:22:55 -0300
To: david.at.boomer.org
Subject: Re: PharmPK Bioequivalence studies - healthy vs patient
The following message was posted to: PharmPK
We routinely use healthy volunteers for bioequivalence study of
retroviral drugs (protease inhibitors or transcriptase reverse
inhibitors). We generally performe single dose administration of the
two formulations.
Gilberto De Nucci
Cartesius Analytical Unit
1524 Prof Lineu Prestes Ave
Sao Paulo - SP
Brazil
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Vanitha:
Hi! Are you referring to the protease inhibitors only or are you also
referring to the first series of compounds for HIV treatment including AZT?
Chetan
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Chetan,
Unless there is a safety concern for using the drug in healthy subjects (as may
be the case for some anti cancer drugs)or if there is reason to believe that PK
is significantly different between the patient population and healthy subjects,
single dose BE studies can be conducted in healthy volunteers.
Vanitha
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