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Dear, Dr. Holford,
I have many problems with the the pharmacodynamics of quinidine.
Is the effect (delta QT interval) dependent on concentration of the parent
drug (free or total?) or metabolite (3-OH-quinidine)?
Shoud I using for this analysis Cmax or AUC? What is better? May be Cmax
metabolite/Cmax parent drug or AUC metabolite/AUC parent drug ratios?
The propose of my study is to compare the pharmacodynamics of quinidine
(tablet, as usual) and prolonged form of this drug. What do you think about
this problem? Is it really interesting?
Thank you for your attention.
Sincerely yours,
Irene Lubenko, MD
nancy.at.com2com.ru
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"nancy (by way of David_Bourne)" wrote:
> I have many problems with the the pharmacodynamics of quinidine.
> Is the effect (delta QT interval) dependent on concentration of the parent
> drug (free or total?) or metabolite (3-OH-quinidine)?
I have no reason to doubt standard pharmacological theory that
asserts the QT changes are due to unbound quinidine. There are
additional effects due to quinidine metabolites. Vozeh et al. have
demonstrated 3-OH-Q is active but Q-N-oxide is not.
Vozeh S. Bindschedler M. Ha HR. Kaufmann G. Guentert TW. Follath F.
Pharmacodynamics of 3-hydroxyquinidine alone and in combination with
quinidine in healthy persons. American Journal of Cardiology.
59(6):681-4, 1987 Mar 1.
Ha HR. Vozeh S. Uematsu T. Guentert TW. Follath F. Kinetics and
dynamics of quinidine-N-oxide in healthy subjects. Clinical
Pharmacology & Therapeutics. 42(3):341-5, 1987
> Shoud I using for this analysis Cmax or AUC? What is better? May be Cmax
> metabolite/Cmax parent drug or AUC metabolite/AUC parent drug ratios?
I see little point in using Cmax or AUC to describe the effects of
quinidine. The time course of QT changes is clearly related to the
whole time course of quinidine concentration. If you are using QT
then you can make lots of measurements very easily and cheaply. Why
limit yourself to single values derived from the concentration
profile?
Holford NHG, Coates PE, Guentert TW, Riegelman S, Sheiner LB. The
Effect of Quinidine and its Metabolites on the Electrocardiogram and
Systolic Time Intervals: Concentration-Effect Relationships. Brit. J.
Clin. Pharmac. 1981; 11: 187-195
> The propose of my study is to compare the pharmacodynamics of quinidine
> (tablet, as usual) and prolonged form of this drug. What do you think about
> this problem? Is it really interesting?
There might be some differences in formation rate of 3-OH-Q depending
on the Q formulation but *I* don't personally find the
pharmacodynamics of different formulations of Q "really" interesting.
Why are *you* interested?
--
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.html
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This message was sent by exfamadu.aaa.savba.sk on Oct 23rd, 1999
There is a possibility to model the relationship between these
two time profiles (and in general between many other time
profiles e.g. between a drug concentration-time profile and a
time course of a biomarker), even without any prior
information about the model structure and order, using our software
employed for example in: Dedik L, Durisova M., Comput. Meth.
Programs, Bio-Med., 51, 1996, 183-192.
Best regards,
Maria Durisova
Dr.Maria Durisova, PhD
Scientific Secretary
Institute of Experimental Pharmacology
http://kam.vm.stuba.sk/~dedik
Slovak Academy of Sciences
SK-842 16 Bratislava
Slovak Republic
Phone/Fax:00421 7 5477 5928
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Dear all,
thank you for the answers to my questions about pharmacodynamics of Q and
3-OH-Q.
Irene Lubenko, MD
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