PharmPK Discussion - Which is the best method to examine fraction absorbed in rats?

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On 15 Apr 2004 at 04:17:31, Garcia PK (garcia_pk.aaa.yahoo.com) sent the message

Dear All:
As I know there are two methods to examine the fraction of oral dose
absorbed (aka gastrointestinal bioavailability) in rats:
Method #1: Administer compound orally and sample blood from jugular
vein. Administer compound in hepatic portal vein and sample blood from
jugular vein. Administer compound by IV route (tail vein) and sample
blood from jugular vein. Based on these 3 AUC valuescalculate
fraction bioavailable in the portal vein (Fgut),hepatic extraction
ratio and total absolute bioavailability.
Method#2: Administer compound by PO route and sample simultaneously
from portal vein and jugular vein.Administer compound by IV. This
gives total absolute bioavailability and a direct measurement of Fgut.
Question:
(1) Which is the best method?
(2) Has anyone done comparison of both methods and found them to be
similar?
Thanks in advance for your reply.
Garcia.

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On 17 Apr 2004 at 12:44:00, "Bhattaram, Atul" (BhattaramA.aaa.cder.fda.gov) sent the message

Hello Garcia
You can get reasonable information if you can compare data after oral vs
intravenous vs intraperitoneal administration. To cannulate or
administer
the drug in portal vein can
be quite challenging.
Venkatesh Atul Bhattaram
Pharmacometrics
OCPB, FDA

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