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[db - I've removed the figure in the attached document - I may try putting
it online - please ask Dr Calvo directly for a copy until then]
Dear Colleagues
I would like to put forward a question looking for an answer from you.
We have performed a bioequivalence study between two lovastatine tablet
formulations. We have taken blood samples from 36 healthy volunteers
between 0 and 24 hours. Both formulations are equivalent regarding Cmax,
Tmax and AUC0-24. Nevertheless, we have found that surprisingly (we have
not found previous descriptions of it) there are a substantial proportion
of kinetic curves that show late raising blood levels from 10-12h to 24h.
Does anybody have previously seen this fact for lovastatine?
Does anybody know which would be the best method for AUC extrapolation to
infinite? An example is given in the attached file.
Hoping to hear from you soon
Yours sincerely
Gonzalo Calvo
email: gcalvo.aaa.hsp.santpau.es
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[db - This message is now online at
http://www.boomer.org/pkin/images/calvo990310.html with the image/graph]
Dear Colleagues
I would like to put forward a question looking for an answer from you.
We have performed a bioequivalence study between two lovastatine tablet
formulations. We have taken blood samples from 36 healthy volunteers
between 0 and 24 hours. Both formulations are equivalent regarding Cmax,
Tmax and AUC0-24. Nevertheless, we have found that surprisingly (we have
not found previous descriptions of it) there are a substantial proportion
of kinetic curves that show late raising blood levels from 10-12h to 24h.
Does anybody have previously seen this fact for lovastatine?
Does anybody know which would be the best method for AUC extrapolation to
infinite? An example is given in the attached file.
Hoping to hear from you soon
Yours sincerely
Gonzalo Calvo
email: gcalvo.-at-.hsp.santpau.es
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[A few replies - the figure is online - db]
Date: Wed, 10 Mar 1999 09:10:55 -0800
From: TM Gilman
Reply-To: tmgilman.at.ibm.net
Organization: Simulations Plus, Inc.
X-Accept-Language: en
MIME-Version: 1.0
To: PharmPK.aaa.pharm.cpb.uokhsc.edu
Subject: Re: PharmPK Lovastatine AUCs
I would like to see the figure you mention - please send it as an email
attachment. Thanks, Tom Gilman
--
Thomas Gilman, M.S., Pharm.D.
Life Sciences, Simulations Plus, Inc.
1220 West Avenue J, Lancaster, CA 93534
voice (888) 266-9294 x239, fax (805) 266-9394
gilman.-at-.simulations-plus.com,
---
http://www.simulations-plus.com Date: Wed, 10 Mar 1999 13:08:21 -0800 (PST)
From: zbenzvi.-at-.bgumail.bgu.ac.il
To: PharmPK.-a-.pharm.cpb.uokhsc.edu
Subject: Re: PharmPK Lovastatine AUCs
X-Sender: zbenzvi.at.bgumail.bgu.ac.il
MIME-Version: 1.0
Hello Dr Calvo
Could you please tell me by what method did yoy analyze
lovastatin? is it mass spectrometry or biological assay?
Sincerely
Zvi Ben-Zvi
---
From: "mmiller"
To:,
"Multiple recipients of PharmPK - Sent by"
Subject: Re: PharmPK Lovastatine AUCs
Date: Wed, 10 Mar 1999 20:15:07 -0500
MIME-Version: 1.0
X-Priority: 3
My educated guess is entero-hepatic recirculation but I admittedly don't
have any research or other references on lovastatin to back this up.
Garry Miller, R.Ph.
Irondale Farm
Woolwich, Maine
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Hello!
I have a comment on data extrapolation.
Extrapolation of the data you have is pure nonsense. Whatever method you use,
it can not provide results that have any significance, since you have none
other information on what happens after 24h but the fact that concentration
will eventually drop to 0 and some vague speculations on how fast it will
happen. I think you have two possibilities. You can use the information you
already extracted out of this data or repeat the measurements, this time
using longer observation interval. Otherwise, I'm afraid the results may not
show realistic picture of lovastatine PK.
Sincerely
Ales
as. Ales Belic dipl. ing.
Laboratory of Modeling, Simulation, and Control
Faculty of Electrical Engineering
University of Ljubljana
Slovenia
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[Two more replies on this topic - db]
Date: Fri, 12 Mar 1999 10:42:34 +0100 (MET)
From: Maria Durisova
To: PharmPK.at.pharm.cpb.uokhsc.edu
Subject: Re: PharmPK Lovastatine AUCs
Dear Gonzalo,
I assume that your measurements are correct. If so, I would
recommend to perform the study with the two formulations
using a modified sampling schedule, i.e. with
sampling between 12-24h and after 24h, to identify
possible additional peaks in the profiles. Models
of profiles containing two or more peaks can be found using our
software named CXT (a version of it is available via PharmPK), and
these models can be used for subsequent bioequivalence
evaluations.
Best regards,
Maria
**************************************
Dr. Maria Durisova PhD
Scientific Secretary
Institute of Experimental Pharmacology
Slovak Academy of Sciences
Bratislava, Slovak Republic
---
From: "Sasso, Patrick [PRI]"
To: "'PharmPK.at.pharm.cpb.uokhsc.edu'"
Subject: RE: PharmPK Re: Lovastatine AUCs - repost with URL
Date: Fri, 12 Mar 1999 09:44:11 -0500
MIME-Version: 1.0
Is it possible that this person has his time points reversed, how is that an
oral dose can show increasing drug level with time after 8 hours or so, this
happened to me once and it turned out that the blood samples were labelled
backwards with regard to their time points.
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