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I need some clarifications:
1)What are the factors affecting blood levels (and AUC) when a
compound is given
IV versus when given IP.
2)When can the AUC IP be greater than AUC IV
Please answer at:
trccr.at.hotmail.com
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I need some clarifications:
1)What are the factors affecting blood levels (and AUC) when a
compound is given
IV versus when given IP.
2)When can the AUC IP be greater than AUC IV
Please answer at:
trccr.at.hotmail.com
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The following message was posted to: PharmPK
1. If the drug undergoes first pass extraction, then AUCs and blood
levels will be lower after IP. There might also be absorption issues, F
may be < 1
2. AUC IP > AUC IV is possible if there is considerable enterhepatic
recycling , which is also route dependent.
Hope this helps.
Srikumaran K. Melethil, Ph.D., JD (August 2001)
Professor, Pharmaceutics and Medicine
University of Missouri- Kansas City
203B Katz Hall (School of Pharmacy),
Kansas City, MO 64110
Phone: voice- 816-235-1794; fax - 816-235-5190
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[A few replies - db]
From: YChugh.-a-.wockhardtin.com
Date: Wed, 4 Jul 2001 06:59:09 +0000
To: david.aaa.boomer.org
Subject: Re: PharmPK IV versus IP
The following message was posted to: PharmPK
1) AUC ip should be less than AUC iv, because of : First pass metabolism
encountered by ip route and possible incomplete absorption. Check the
specificity of your analytical method. Use LC/MS/MS which would give you
better results.
2) Blood levels and AUC depends on many factors like volume of
distribution, tissue penetration, lipophilicity of the compound and of
course elimination kinetics.
Yati Chugh
---
From: JYOTI PALIWAL
Date: Wed, 4 Jul 2001 18:03:57 +0530
To: david.-at-.boomer.org
Subject: Re: IV versus IP
The following message was posted to: PharmPK
Stability of the drug in peritoneal fluid, first pass effect and EHC can
result AUC value different than IV route. Drugs with Molecular weight >300
are likely to undergo EHC in rat when given orally or IP. This might result
in AUC higher than IV route.
Hope this helps
Dr. Jyoti Paliwal
---
From: "atul"
Date: Wed, 4 Jul 2001 10:19:48 -0700
To: david.at.boomer.org
Subject: Re: PharmPK IV versus IP
The following message was posted to: PharmPK
Hello
Two things are possible:
1. The AUC after ip might be less than after iv if there is a good hepatic
extraction (includes biliary excretion etc)
2. If you are infusing a very high amount of drug intraperitoneally you
might be saturating the enzymes in the liver locally. This might (depending
on the nature of the drug) increase the AUCip (since all drug enters the
portal vein leading to the liver) in comparison to AUCiv. Although I am not
aware of any papers reporting this type of observation I would be happy if
somebody can suggest some reference where a similar situation has been
observed.
Also a study with wide dose ranges will help you understand more as to how
your drug is being handled by liver etc.
Hope this helps
Atul
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