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Dear friends,
I need some information about drugs showing sigmoid curve type of
pharmacokinetics. What are these drugs and what is the relationship with
pharmacodinamic parameters.
Regards,
Jayant
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[Two replies - db]
From: "Nick Holford"
To:
Subject: Re: PharmPK Re: drugs having sigmoid curve
Date: Tue, 27 Oct 1998 06:34:40 +0200
MIME-Version: 1.0
X-Priority: 3
>I need some information about drugs showing sigmoid curve type of
>pharmacokinetics. What are these drugs and what is the relationship with
>pharmacodinamic parameters.
As far as I am aware there is no such thing as a "sigmoid" pharmacoKINETIC
curve. This term is used to describe pharmacoDYNAMIC curves.
The conc vs effect predictions of the classical Emax model derived from the
law of mass action will appear sigmoid when log(conc) is used for a plot. It
is also possible to describe the conc-effect relationship with a sigmoid
Emax model. If the sigmoidicity parameter (Hill coefficient) is > 1 then a
plot of conc vs effect using a linear conc will appear sigmoidal.
--
Nick Holford
Dept Experimental & Clinical Pharmacology
University of Natal Medical School, Durban, South Africa
n.holford.-at-.auckland.ac.nz
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Date: Tue, 27 Oct 1998 10:40:01 -0500
From: "Vakily, Majid {RDT~Nutley}"
Subject: RE: PharmPK Re: drugs having sigmoid curve
To: "'PharmPK.-at-.pharm.cpb.uokhsc.edu'"
Mime-Version: 1.0
Dear Jayant,
I am not sure what do you mean by drugs showing sigmoid type curve.
However, I think you mean the relationship between drug concentration
(at steady-state) vs. observed effect. Drugs' PK never show sigmoid
pattern. But, drug conc vs. effect or toxicity may exhibit sigmoid Emax,
Emax, linear..... relationship.
Regards
Majid
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[Two more replies - db]
Reply-To: "Thomas Senderovitz"
From: "Thomas Senderovitz"
To:
Subject: Sv: PharmPK Re: drugs having sigmoid curve
Date: Tue, 27 Oct 1998 19:20:04 +0100
MIME-Version: 1.0
X-Priority: 3
Dear Jayant,
If you think about plasma concentration-time curves in a double arithmetric
plot, the kind of curves you describe is most likely due to zero order
kinetics (the curve will be sigmoid in a semilogartihmic plot). The reason
for zero order kinetics is most often saturation of the enzymes responsible
for the metabolism of the drug.
Kind regards,
Thomas Senderovitz, MD.
E-mail: senderovitz.-at-.dadlnet.dk
---
From: "Piotrovskij, Vladimir [JanBe]"
To: "'PharmPK.aaa.pharm.cpb.uokhsc.edu'"
Subject: RE: PharmPK Re: drugs having sigmoid curve
Date: Wed, 28 Oct 1998 10:27:29 +0100
MIME-Version: 1.0
It is possible to have a kind of sigmoidicity in a plasma concentration-time
profile after oral administration. Namely, the initial concentration rise
may be slow and then it becomes faster. The reason is that the hepato-portal
system may retain some drugs. The phenomenon can be modelled by including
one or more compartments between the absorption compartment and the central
compartment.
Vladimir
----------------------
Vladimir Piotrovsky
Clinical Pharmacokinetics
Janssen Research Foundation
2340 Beerse, Belgium
e-mail: vpiotrov.-at-.janbe.jnj.com
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The terms pharmacoKINETICS and pharmacoDYNAMICS have been
used extensively for a long time indiscriminately for drugs
and a large number of other biologically active substances to
distinguish the description of their fate from that of the
their effect. However, considered from the point of view of
the theory of the dynamic systems and exactly speaking, if
the behavior of the systems describing the drug fate and the
systems describing the drug effect is DEPENDENT on the state
of these systems (which is the usual case) both groups of
these systems are DYNAMIC systems.
The well developed theory of the dynamic systems is
mathematically elegant and is the basis for several modeling
approaches, including those used in pharmacokinetics. In the
light of this fact, it may be useful for pharmacokineticists
to reconsider the above mentioned terminology and to adopt
the exact terminology of the theory of the dynamic systems.
Namely, instead of the term "the pharmacoKINETIC curve" to
use the term "the response of the system describing the drug
fate" and instead of the term "the pharmacoDYNAMIC curve" to
use the term "the response of the system describing the drug
effect".
:-)
1. Dedik L., Durisova M., Int. J. Bio-Med. Comput., 39, 1995,
231-241.
2. Dedik L., Durisova M., Comput. Methods Programs Biomed.,
51, 1996, 183-192.
Dr.Maria Durisova,PhD
Institute of Experimental Pharmacology
Slovak Academy of Sciences
and
Assoc.Prof.Ladislav Dedik,PhD
Department of Automation and Measurement
Slovak Univeristy of Technology
Slovak Republic
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While it is important to be explicit and precise when we communicate, most
of the subscribers to this list may opt for the term "PK/PD" rather than
"TROTSDTDF/ TROTSDTDE" : -)
Jeff Wald
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[Two replies - I still prefer PK/PD :-) - db]
From: "Nick Holford"
To:
Subject: Re: PharmPK Re: PharmPH drugs having sigmoid curve
Date: Sat, 31 Oct 1998 06:37:11 +0200
MIME-Version: 1.0
X-Priority: 3
But why not use "TF/TE" :-)
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From: Maria Durisova
Subject: Re: PharmPK
To: PharmPK.at.pharm.cpb.uokhsc.edu
Date: Sat, 31 Oct 1998 14:21:51 +0100 (MET)
MIME-Version: 1.0
And what about
"DF/DE" ? : -)
Maria Durisova
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