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Dear all,
Could anyone name a few drugs with clinically important lung first pass
metabolism (if there's any)?. Melmon and Morelli's clinical pharmacology
says that this first pass is only clinically relevant when a drug is given
by a central catheter, but I don't know any example.
Thank you (and please forgive my ignorance!).
yours,
Facundo Garcia Bournissen.
Dept. Pharmacology, School of Medicine, University of Buenos Aires.
Paraguay 2155, Piso 16,
(1121) Capital Federal,
Argentina.
E-mail: Bournissen.at.intramed.net.ar
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Inhaled steroids e.g. budesonide have important pulmonary first pass.
This is an advantage in minimising systemic effects. This drug was
not available when M&M wrote their classical book.
--
Nick Holford, Divn Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand
email:n.holford.-at-.auckland.ac.nz tel:+64(9)373-7599x6730 fax:373-7556
http://www.phm.auckland.ac.nz/Staff/NHolford/nholford.htm
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Yep, I hadn't thought of that. Thanks!.
Still, I was looking for a drug that had lung first pass metabolism when IV
infused. Any examples out there?.
(now that I come to think of it, would IV budesonide, or fluticasone, have
such a big lung first pass metabolism as they do when inhaled??).
By the way, M&M have a new edition from last year!. And a very nice one
too.
Facundo Garcia Bournissen.
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Hi,
Propofol is a well known drug to be metabolised by
hepatic first pass .
Please check the following reference:
Kuipers JA, Boer F, Olieman W, Burm AG, Bovill JG;
Anesthesiology 1999 Dec;91(6):1780-7,
First-pass lung uptake and pulmonary clearance of
propofol: assessment with a recirculatory indocyanine
green pharmacokinetic model.
Besides , literature indicates pulmonary first pass of
ciprofloxacin and some organophosphates.
Also,the opiate fentanyl shows 75 % lung 1st pass
(http://www.users.dircon.co.uk/~rosebud/drugs/Opioids.html)
Hope this helps
Santosh Dixit
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Please note, fentanyl has a rapid and extensive (75%) lung UPTAKE not
metabolism, which is largely hepatic. The drug is washed out of the lung for
systemic effect.
Tom Torda
Anaesthesia,
Prince of Wales Hospital,
University of New South Wales,
Sydney, OZ
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I have to correct the statement that budesonide is subjected to first pass
metabolism in the lung. This is not correct. Budesonide is subjected to
extensive first pass metabolism in the liver but not in the lung (not even
after inhalation). Furthermore, I don=B4t think that the statement that
fluticasone would be subjected to first pass metabolism in the lung is
correct either.
Paul Andersson
AstraZeneca
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Alprostadil.
Supong
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Thanks everybody for the rapid answers about my question regarding
drugs with extensive (or at least clinically important) first pass
metabolism in the lungs!.
I guess that Paul Andersson is right (I'm beating myself with Goodman
& Gilman's after I send this mail) about fluticasone too. It doesn't
seem to have lung first pass... (at least G&G says its extensively
metabolised in the liver)...
Thanks a lot again.
Facundo Garcia Bournissen.
e-mail: bournissen.aaa.intramed.net.ar
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Dr. Bournissen,
The lungs have been associated with a significant first-
pass uptake with intravenous propranolol. Geddes et al measured
the first-pass extraction of intravenous propranolol in patients
undergoing cardiac catheterization, and found ~75% first-pass
extraction in patients not previously exposed to the drug. This
process is partly saturable by normal therapeutic doses, as the
first-pass extraction decreases to ~33% in patients receiving oral
propranolol. Tissue distribution studies have found that the
lungs accumulate propranolol to a remarkable extent, approaching
a tissue/plasma ratio of 250. The lungs have also been shown to
accumulate large quantiies of lidocaine, imipramine, amphetamine
and chlorcyclizine, as well as other amines. Some drugs are
metabolzed as well as accumulated, such as nortriptyline, methadone
and chlorpromazine.
Mike Leibold, PharmD, RPh
ML11439.-a-.goodnet.com
References
1) Benet, L.Z. et al, Pharmacokinetic Basis for Drug Treatment,
Raven Press, New York 1984
2) Gibaldi, M., Prescott, L., Handbook of Clinical Pharmacokinetics,
ADIS Press, 1983
3) Geddes, D. et al, First-pass uptake of 14C-propranolol by the lung,
Thorax 1979;34:810-813
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