Back to the Top
Dear sir,
I have a question. In light of the recognition of endogenous
digoxin-like substance levels being present in patients with renal
insuffiency, is it of value to take pre-treatment digoxin levels?
Our research has shown that
although these endogenous compounds have been recognized and quantified,
there is no consensus on what to do with these values. It seems as if the
role of endogenous digoxin-like substance in pathologies treated with
digoxin are not clear. I would appreciate any and all input.
Thank you very much in advance.
Ash Patel.
ash.at.oaktree.net
Back to the Top
Ash,
Yes, it may be warranted to measure a digoxin serum concentration prior to
initiating therapy in patients known to exhibit significant levels of DLIS
(renal failure, hepatic failure, neonates, pregnant women in the third
trimester). However, the only benefit to obtaining these pre-therapy
concentrations will be to establish the presence of DLIS. There is no
evidence that DLIS and digoxin concentrations are additive. (ie, if the
therapeutic range is established as 0.5-2 ng/ml and a renal failure patient
has a pre-therapy digoxin concentration of 0.5 ng/ml, it is NOT correct to
adjust that patient's therapeutic range to 1-2.5 ng/ml) Rather, the
knowledge that this patient exhibits significant levels of DLIS may help to
explain in the future why no signs of toxicity are present if a steady-state
supra-therapeutic concentration is obtained.
Before adjusting a patient's digoxin dose in response to a sub- or
supra-therapeutic concentration, a clinician needs to take many factors into
account, such as the time the last dose was administered (and whether the
sample was collected in the distribution phase), whether steady-state has
been achieved, the patient's eletrolyte status, and most importantly, the
patient's clinical response. Some patients may require what appears to be a
supra-therapeutic concentration to acheive a therapeutic response, while
others may exhibit toxicity at "therapeutic" concentrations. The presence
of DLIS is just one more factor which makes it necessary to treat the
patient and not the drug concentration.
Regards,
Kristine Radomski, Pharm.D.
Fellow in Clinical Pharmacokinetics/Pharmacodynamics
University of North Carolina at Chapel Hill
and
Glaxo Wellcome, Inc.
Back to the Top
Dear Ash and all:
Digoxin is an extremely interesting drug. In managing digoxin
therapy for
patients, we have been most impressed with the "population" model made by
Reuning and colleagues at Ohio State back in 1973, in which he showed much
better correlation of the inotropic effect with computed concentrations in
the peripheral nonserum compartment that with the serum concentrations.
We have used this model now for over 20 years in the USC*PACK programs,
and like it a lot. Clinical response correlates much better with computed
concentrations in the peripheral compartment than with the raw data of the
serum levels, though these are required to make the Bayesian posterior
individualized PK model.
We have seen that a patient can be in atrial fib at one time with a
serum
level of 1.0, for example, and in sinus rhythm at another with the
identical 1.0 serum level, as things were not at all in a steady state, and
the samples were drawn at somewhat different times after their respective
doses. We have found that use of such a model with a peripheral compartment
lets you see many things that are simply not visible otherwise. We have had
good experiences in maintaining conversion of AF to RSR after the use of
these models, where the raw data of the serum concentrations themselves was
not helpful at all.
In addition, we have seen that when a patient is on digoxin and
quinidine,
that if you add up the total amount of digoxin in both the central (serum)
and peripheral compartments, that patients usually do NOT have greater
amounts of digoxin in their bodies, due to the very reduced peripheral
compartment uptake by most tissues - quite a surprise.
All this is simply meant to say that there is more to digoxin than the
serum levels. DLIS IS important. So is the PK model that the serum data can
be used to make, and it gives insights into a patient's problems and needs
that raw data of serum levels alone cannot show to us.
I make this point because it seems that few have considered the
utility of
the model of Reuning and colleagues, and of modeling a peripheral
compartment for digoxin and relating it to at least an important part of
the patient's clinical response, and I would suggest that it is a most
useful way to perceive the action and clinical effects of digoxin, and to
relate the model to the clinical bahevior of the patient, to better assess
his/her sensitivity to the drug, and to compute the dosage regimen needed
to achieve desired target goals in the peripheral compartment.
Sincerely,
Roger Jelliffe
************************************************
Roger W. Jelliffe, M.D.
USC Lab of Applied Pharmacokinetics
CSC 134-B, 2250 Alcazar St, Los Angeles CA 90033
Phone (213)342-1300, Fax (213)342-1302
email=jelliffe.at.hsc.usc.edu
************************************************
Take a look at our Web page for announcements of
new software and upcoming workshops and events!!
It is http://www.usc.edu/hsc/lab_apk/
************************************************
PharmPK Discussion List Archive Index page
Copyright 1995-2010 David W. A. Bourne (david@boomer.org)