Back to the Top
Dear all,
I would appreciate any comment on the following:
Let's consider a drug with two-compartmental pharmacokinetics
administered by IV infusion. Distribution occurs as soon as the infusion
has started and goes on during all the infusion period.
Can the distribution phase be masked by a prolonged infusion? In what
particular cases?
A very practical example: the distribution phase of vancomycin is of
about 2-3 hours. Shall we consider that distribution is accomplished 2-3
h after the end or after the beginning of the infusion?
Many thanks for any advice.
Back to the Top
[Three replies - db]
Date: Tue, 14 Sep 1999 09:07:12 +1200
From: Nick Holford
X-Accept-Language: en
To: PharmPK.at.boomer.org
Subject: Re: PharmPK Distribution phase
Distribution (and elimination) are occurring all the time. There is no
"end" to the distribution of the drug.
I think you may be asking for some more practical advice however e.g. at
what time after a 3 h infusion could one draw a blood sample for TDM and
be able to assume one compartment kinetics?
Is this what you want to know?
--
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, Private Bag 92019, Auckland, New Zealand
email:n.holford.-a-.auckland.ac.nz tel:+64(9)373-7599x6730 fax:373-7556
http://www.phm.auckland.ac.nz/Staff/NHolford/nholford.htm
---
Date: Mon, 13 Sep 1999 15:46:39 -0700
From: "David Nix, Pharm D."
Organization: College of Pharmacy
To: PharmPK.aaa.boomer.org
Subject: Re: PharmPK Distribution phase
This problem can be simplified by considering an infusion to be multiple
bolus doses. If the infusion is 100 mg over 50 minutes, then this would
be similar to giving a 2 mg bolus every minute. Suppose that the
distribution half life is 10 minutes. Distribution for drug given
during the first 10 minutes would be nearly complete by the end of the
infusion. However, distribution of drug given within the last few
minutes of the infusion would be just starting. Whether the
distribution phase is masked by the infusion will depend how prominent
the distribution is after a bolus dose and how many "2 mg bolus doses"
are still undergoing distribution (this is based on distribution
half-life).
For a two compartment model where C(t)=A*exp(-alpha*t)+B*exp(-beta*t), a
large A coefficient compared to B coefficient would be associated with a
prominent distribution phase. The superposition principle will apply to
the repeated small "bolus doses".
---
From: =?ks_c_5601-1987?B?ueix1by3?=
To:
Subject: Re: PharmPK Distribution phase
Date: Tue, 14 Sep 1999 09:01:42 +0900
X-Priority: 3
Dear, all
It will be helpful to see Fig 2.10 and relevant text at page 71 of
Gibaldi & Perrier, Pharmacokinetics, 2nd ed. revised and expanded.
Marcel Dekker, 1982
Kyun-Seop Bae MD
Department of Pharmacology
Seoul National University College of Medicine
&
Clinical Pharmacolgy Unit
Seoul National University Hospital
Back to the Top
Just to clarify David's last comment
It is not just the large A coefficient that is important it
is how large A/alpha is compared to B/beta.
Regards
Steve
=====================
Stephen Duffull
School of Pharmacy
University of Manchester
Manchester, M13 9PL, UK
Ph +44 161 275 2355
Fax +44 161 275 2396
PharmPK Discussion List Archive Index page
Copyright 1995-2010 David W. A. Bourne (david@boomer.org)