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Has anyone any information on the pharmacokinetics/dynamics of propofol and
remifentanil during cardiopulmonary bypass. We use them and they work well
but I am just wondering what is going on at the the efect site in terms of
levels. I have heard that bypass is associated with some form of enhanced
bioavailability due to alterations in Vd. Any help?
Please reply direct to andrew.ferguson.-a-.virgin.net
Thanks in advance
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[Two replies - db]
Date: Wed, 02 Dec 1998 21:06:35 -0500
From: "Wagner, Bertil K {PDRD~Nutley}"
Subject: RE: PharmPK Re: Propofol/remifentanil on CPB
To: "'PharmPK.aaa.pharm.cpb.uokhsc.edu'"
Mime-Version: 1.0
Dear Andrew,
CPB is associated with an increase in body water volume as well as a
significant decrease in plasma proteins and plasma protein binding.
Therefore, expect an increase in volume of distribution. Also, normal
elimination/excetion pathways are impaired due to decreased tissue
perfusion. For propofol there has been mention of extrahepatic (pulmonary?)
elimination. This would probably also be decreased since the lungs are
excluded from the general circulation during CPB. Therefore, anticipate
decreased total plasma concentrations during but slower elimination and
some drug accumulation following CPB. The effect of propofol is probably
not affected by CPB since the effect of propofol is less related to drug
elimination than to drug distribution. The same probably holds true for
remifentanil since its metabolic pathways probably are not affected by CPB.
The pharmacokinetics of drugs during CPB have been very well described by
FO Holley in the journal Clinical Pharmacokinetics and the information
updated in the same journal just a few years ago.
Bertil Wagner, Pharm.D., FCCM
Hoffmann-La Roche, Inc.
340 Kingsland Street
Nutley, NJ 07110
(972) 562-5515
bertil_k.wagner.-a-.roche.com
---
Reply-To:
From: "Steven L. Shafer"
To:
Cc:
Subject: RE: PharmPK Re: Propofol/remifentanil on CPB
Date: Thu, 3 Dec 1998 06:47:37 -0800
MIME-Version: 1.0
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Dear Andrew:
You will find the pharmacokinetics of propofol during CPB described
in "The pharmacokinetics of propofol in adult patients undergoing
coronary revascularization." Anesthesiology 84:1288-1297, 1996.
I am not aware of any publications on the pharmacokinetics of
remifentanil during CPB.
> I am just wondering what is going on at the effect site in
> terms of levels. I have heard that bypass is associated with
> some form of enhanced bioavailability due to alterations in Vd.
> Any help?
There are several concepts mixed together here that are worth
keeping separate. First, "enhanced bioavailability" would usually
refer to some non-intravenous route of administration. I think what
your are saying is that the plasma levels during an infusion may
be higher, due to a decreased volume of distribution. I'm not aware
of any data that this is true. Given the potential of the bypass machine
for binding drug, if anything I would expect the volumes of distribution
to increase, leading to lower plasma concentrations during an infusion
to steady state. Once steady state is reached, then the concentrations
are, of course, determined solely by clearance.
As for the effect site, I'm not aware of any data suggesting that the
relationships between plasma and effect site drug concentrations are
influenced by CPB. Now there may be a difference in the relationship
between effect site drug concentration and drug effect. For example,
cold itself is an anesthetic. Thus, one might expect to see increased
potency for propofol in the cooled patient on CPB, because of interactions
between brain temperature and the propofol concentration vs effect
relationship.
I hope this is helpful.
Steve Shafer
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