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The following message was posted to: PharmPK
Hi, All:
I have met some drugs which have strange IV profiles. My blood
collection time is 2, 10, 20 min .....; Normally the conc. of 2 min
will be higher than 10 min, but in my experiment, the conc. of 10 min
is higher than 2min. In my past few experiments, I also met some
drugs like this strange IV profiles such as some antibiotic drugs.
Does someone else meet the phenomenon like this and know how to
explain this phenomenon? Thanks!
Jian wang
Assistant Researcher of Dept. DMPK
Hutchison Medipharma Limited
Building 4, 720 Cai Lun Rd.
Z.J.Hi-Tech Park,
Shanghai, China 201203
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The following message was posted to: PharmPK
dear jiang,
what formulation did you use and where did you administer it? In case
of a
highly viscous solution (e.g. > 50% of PEG400), a administration into
small
vessels (e.g. tail vain of rats), it may be that the compounds dilution
from the formulation takes longer than 2 min.
regards,
Philip
**
Dr. Philip Lienau
Schering AG
Research Pharmacokinetics
Tel.: +49 - 30 - 468 - 18507
Fax: +49 - 30 - 468 - 12238
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The following message was posted to: PharmPK
Dear Jian,
as a formulation scientist I would really appreciate to know which
kind of formulation was used for this experiment ?
One (out of a lot of) explanation could be based on a non-relevant
dosage form which would cause precipitation and re-dissolution of the
drug.
Could you explain your formulation strategy ?
Thanks a lot,
Frederic Doc
ACRITER - drug discovery consulting
www.acriter-consulting.com
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The following message was posted to: PharmPK
Dear Jian,
unfortunately some interesting information is missing in your email.
In human beings, this finding is not so strange as you mention.
Usually drugs are administered in the periphery of the body (e.g. an
arm) and than you need some minutes to distribute the drug in the
body system. Blood circulations time is estimated to be in the range
of 5 minutes.
The slower the drug is infused, the faster you reach homogenous
distribution of blood in the body system (measured from end of
infusion/injection). If you administer the drug as a bolus, you might
reach homogenous concentrations even after 10 to 20 minutes, if you
administer the drug slowly over several minutes/hours, you will reach
homogenous concentrations already a couple of minutes after stopping
the infusion.
I do not have any experience in animals but assume that this will be
very similar in these species.
Best regards,
Christian
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Dear Wang Jian,
We have seen this in furosemide in infusion to patients. And in
DRUG METABOLISM AND DISPOSITION Vol. 26, No. 5,
MECHANISM OF ASCORBIC ACID ENHANCEMENT OF THE BIOAVAILABILITY AND
DIURETIC EFFECT OF FUROSEMIDE
By MYUNG G. LEE AND WIN L. CHIOU,
this phenomenon has been discussed .
Dr. Sima Sadrai,PhD
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I have seen this with an iv drug I worked on. With a 30 minute
infusion, concentrations were higher at 15 minutes than at 30
minutes. I took this to be due to one of two things: time-dependent
metabolism or time-dependent volume of distribution. Some enzymes,
like serine proteases, are inactive at first and then their Vmax
ramps up so that first you have slow metabolism and then you have
faster metabolism. I had a hard time explaining time-dependent Vd
but I have seen some theoretical papers on it. There is one other
possibility and that is you have saturable transport from the central
compartment to a peripheral compartment.
Good luck identifying the source,
pete
Peter L. Bonate, PhD
Genzyme Corporation
Senior Director, Pharmacokinetics
4545 Horizon Hill Blvd
San Antonio, TX 78229 USA
peter.bonate.at.genzyme.com
phone: 210-949-8662
fax: 210-949-8219
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The following message was posted to: PharmPK
Hi Wang;
It is possible that your drug or drugs have quick distribution phase
need
sometime to equilibrate. Therefore you observed such phenomenone.
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The following message was posted to: PharmPK
Dear Jian!
>Does someone else meet the phenomenon like this and know how to
>explain this phenomenon?
1. Yes ;-)
2. Precipitation, followed by dissolution from the lungs...
best regards,
Helmut
--
Helmut Sch=FCtz
BEBAC
Consultancy Services for Bioequivalence and Bioavailability Studies
Neubaugasse 36/11
1070 Vienna/Austria
tel/fax +43 1 2311746
Web http://BEBAC.at
BE/BA Forum http://forum.bebac.at
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The following message was posted to: PharmPK
Dear All:
Thanks for your responses. I am sorry for not providing enough
informations about my experiment. In this experiment, the object is
rat, and the administration method is IV drug solution via tail. The
formulation is 10% DMSO + 15% Cremophor EL.And I also saw this
phenomenon in beagle dogs which also use the same administration method.
Jian wang
Hutchison Medipharma
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