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The following message was posted to: PharmPK
I am looking for some ethical guideline or experience about safety when
performing antirretroviral bioavailability/bioequivalence studies in
healthy volunteers .
For example, it would not be accepted to administer a drug such as insulin
to a healthy subject, is there any general ethical criteria regarding which
drugs should never be administered to healthy volunteers?
Thanking in advance, regards, Silvia Giarcovich
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The following message was posted to: PharmPK
Silvia,
The use of healthy volunteers in BA/BE studies is routine. However, one
could debate the ethics of performing such a study in HIV-infected patients
who are being administered potentially sub-optimal doses of investigational
drugs, probably as monotherapy! For a short duration study the risk of
resistance appears low, but certainly increases with the duration of study.
regards,
Patrick Smith
SUNY-Buffalo
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The following message was posted to: PharmPK
Silvia
The impression I have got, is that as far as oral administration is
concerned (which would cover most of the BE studies), I think that
there is no commercial drug available that could not be administered
to healthy volunteers for a BE study. On the specific topic of
antiretroviral agents, a quick search on PubMed found close to 60
papers on administration of these drugs to healthy volunteers.
Best wishes
Gilberto De Nucci
Cartesius Analytical Unit
Department of Pharmacology - ICB -USP
Sao Paulo - SP
Brazil
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The following message was posted to: PharmPK
There is no specific guidelines, to my knowlegde, that dictate which drugs
can or can't be given to healthy volunteers. However, FDA, and other
regulatory agencies mention that if the drug is toxic, the study can be done
in patients instead of healthy volunteers. The risk depends on the drugs
itself, the dose, and duration of treatment. Therefore, it has to be
evaluated on a case by case basis.
One caveat is that we sometime mix the therapeutic class with the risk
itself. For HIV drugs, the majority of them can be given to healthy
volunteers as single dose. For anticancer drugs, the majority of them
cannot be given to healthy volunteer due to the risk of carcinogenicity, and
other toxic effects. However, there is some exceptions (e.g.
anti-hormones, antimetabolites).
Eric Masson, Pharm.D.
Scientific Director
Anapharm Inc.
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Dear Eric,
I fully agree with your note on the above subject. I feel it is the moral
responsiblity of the clinical investigator/pharmacologist to weigh the risk
to the subject while studying such toxic drugs in healthy subjects on a
single dose administration, rather than looking at regulatory compliance or
guidances. These things are already covered under GCP.
regards,
rk bangaru
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Another consideration regarding conducting BE studies in HIV-infected
patients relates to concern about withholding drug during washout intervals
and withholding other antiretroviral or OI medications during the study,
with associated risks of resistance development and/or development of OIs,
depending on HIV status and stage of disease. This may be less of an issue
now in some patient segments compared to recent policy of early and
aggressive treatment.
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PharmPK - Discussions about Pharmacokinetics
Pharmacodynamics and related topics
The following message was posted to: PharmPK
There is no specific guidelines, to my knowlegde, that dictate which drugs
can or can't be given to healthy volunteers. However, FDA, and other
regulatory agencies mention that if the drug is toxic, the study can be done
in patients instead of healthy volunteers. The risk depends on the drugs
itself, the dose, and duration of treatment. Therefore, it has to be
evaluated on a case by case basis.
One caveat is that we sometime mix the therapeutic class with the risk
itself. For HIV drugs, the majority of them can be given to healthy
volunteers as single dose. For anticancer drugs, the majority of them
cannot be given to healthy volunteer due to the risk of carcinogenicity, and
other toxic effects. However, there is some exceptions (e.g.
anti-hormones, antimetabolites).
Eric Masson, Pharm.D.
Scientific Director
Anapharm Inc.
---
Also see: http://www.boomer.org/pkin/
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The following message was posted to: PharmPK
There is another real issue, here. Drugs given to healthy volunteers often
have very different kinetics from the same drugs in patients. Whether this
may be the case here, I do not know. None the less, if the study yields
little of real value, it is hard to justify any possibility of adverse
effects in the volunteers.
Studies in the group in which the drugs may be clinically used will be more
relevant in any case.
Tom Torda MD
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