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Hi,
I just needed some commentary/advice on having more circadian
variation (day vs. night) in overall systemic CL under meal intake
condition compared to meal-restricted condition (high variability in
CL between am and pm when dose given after meal compared to dose
given with no meal). Does this make any sense? If so, the only
explanation I can think about is possibly change in liver blood flow
with meal intake (increase blood flow to liver after meal intake).
I appreciate your help
Kamal Dabbah
Reasearch Assisstant
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Kamal,
Would you be able to elaborate more on the dosing? You mention
changes in "systemic CL". Are you giving the compound iv and at 4
different conditions: fed and fasted in the morning, fed and fasted
in the evening and see differences/higher variability in systemic
clearance depending on when the drug is administered? What is the
major eliminating organ for this compound?
Toufigh Gordi
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The following message was posted to: PharmPK
Hello Kamal,
the literature given below by Anders Grahnen from Quintiles , taken from
the PharmPK database (1999) may help you.
best regards
Hans Markus
--
Dr. Hans Markus Bender
Merck KGaA
Institute of Drug Metabolism and Pharmacokinetics
e-mail: hansmarkus.bender.-a-.merck.de
--
On 11 Mar 1999 at 21:54:50, agrahnen.at.qupp.quintiles.com
sent the
message
Hi Maria,
One of the most studied NSAID with respect to
chronopharmacokinetics
is
indomethacin. Several papers has been published in the early
80=B4s.
Results
have been summarized in a proceedings from the FIP congress 1985:
Labrecque
G & M-Belanger: Time-dependency in the Pharmacokinetics and
Disposition of
Drugs. In: TOPICS IN PHARMACEUTICAL SCIENCES 1985 (Eds DD
Breimer, P.
Speiser). Elservier Science Publishers B.V. 1985, pp 167-177.
Best regards
Anders Grahn
Anders Grahnen, Ph.D.
Vice-President R&D
Quintiles AB
Islandsgatan 2
753 18 UPPSALA
SWEDEN
Phone +46 18 680100
Fax +46 18 680150
Email: agrahnen.at.qupp.quintiles.com
[You might try http://www.boomer.org/cgi-bin/htsearch?
method='and'&sort='score'&words=circadian&restrict=http://
www.boomer.org/pkin/ for more information from the archive - db]
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