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Dear All, I am confused about certain aspects of clearance concept.
What is the relationship between clearance and route of
administration? Thanks
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The following message was posted to: PharmPK
Nilanjana,
You ask:
> What is the relationship between clearance and route of
administration?
The simple answer: There is no relationship between the clearance and
route of administration.
Clearance is defined in terms of drug concentration and rate of
elimination:
Rate of Elimination = Clearance * Concentration
The more complicated answer: Because clearance is often estimated
after oral dosing it is impossible to know clearance but only the
ratio of clearance/F where F is the extent of biovailability. F
itself may depend on the dose and/or rate of absorption so the
apparent clearance may vary with dose and rate of absorption.
--
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New
Zealand
n.holford.-a-.auckland.ac.nz tel:+64(9)373-7599x86730 fax:+64(9)373-7090
www.health.auckland.ac.nz/pharmacology/staff/nholford
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The following message was posted to: PharmPK
Clearance, if you mean total body clearance, is the sum of all
clearances in the body system, e.g.
CL(total)=CL(hepatic)+CL(renal)+CL(other). The CL can be changed using
an other route of administration, if the route 'does not include' (or
not include the total extend) the site of clearance. A major impact is
the hepatic clearance, if the drug has a high first pass effect and your
route changes from oral administration to an other route, like
sublingual, rectal, transdermal,... than the total body clearance
decreases.
Willi
--
Willi Cawello
Clinical Pharmacokinetics
Schwarz Pharma AG/UCB Pharma
40789 Monheim am Rhein, Germany
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The following message was posted to: PharmPK
Willi,
I am not sure if I've understood you correctly. You've mentioned that
CL can be changed using another route of administration, and then you
gave the example of the hepatic clearance and its impact on total
clearance if route changes from oral to rectal (or another route). It
appears to me that you are referring to what some people call "oral
clearance" with is not really clearance but CL/F, as Dr. Holford
mentioned. Is that what you meant by your statement?
The actual CL does not change with the route of administration but
the CL/F can, since F can be different for each route. The only
exception that I can think of is when an oral dose of a highly
metablized compound is large enough to saturate metabolism during its
first pass through the liver (free liver conc. >>> Km). In that case
I can see the actual CL from an oral and IV route being different,
although I have never personally seen any examples of this phenomenon.
Regards,
Edgar
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