Re: [NMusers] RE: Estimation of ke0 from raw data

From: <j.h.proost_at_rug.nl>
Date: Mon, 14 Sep 2015 20:49:34 +0200

Dear Jos,

Although you have found a solution already, I would like to point to the
following publication:

Unadkat JD, Bartha F, Sheiner LB. Simultaneous modeling of
pharmacokinetics and pharmacodynamics with nonparametric kinetic and
dynamic models. Clin Pharmacol Ther 1986; 40: 86-93.

If I understand you correctly, this approach is exactly what you were
asking for. The PK, consisting of linear interpolation between the
observations, so purely nonparametric and noncompartmental, is used as
the driving force for the effect compartment concentration Ce with a
first-order rate constant ke0. Plotting Ce versus E gives a hysteresis
plot, and by adjusting ke0 the increasing and declining part of the
curve can be made to collapse. The PD model can be used parametrically
and nonparametrically.

I have applied this approach in several papers, also comparing various
approaches, e.g.

Proost JH, Schiere S, Eleveld DJ, Wierda JMKH. Simultaneous versus
sequential pharmacokinetic-pharmacodynamic population analysis using an
Iterative Two-Stage Bayesian technique. Biopharm Drug Dispos 2007;
28(8): 455-473.


I did not check whether this approach may the same method as used in
Phoenix.

best regards,

Johannes H. Proost
Dept. of Pharmacokinetics, Toxicology and Targeting
University of Groningen
The Netherlands



Lommerse, JPM (Jos) schreef op 8-9-2015 om 15:38:
>
> Hi Brian and others,
>
> Thank you for all your replies. I’ve indeed found a solution in
> Phoenix. Using Phoenix it was fairly simple to get an estimate on ke0
>
> without using any assumption on the PK or PD (no time course PKPD
> model needed), except for the effect compartment itself.
>
> It is a quick manual try-and-error approach to collapse the hysteresis
> PK-PD curve resulting in an estimate for ke0.
>
> Kind regards,
>
> Jos
>
> *From:*owner-nmusers_at_globomaxnm.com
> [mailto:owner-nmusers_at_globomaxnm.com] *On Behalf Of *Sadler, Brian
> *Sent:* Sunday, September 06, 2015 12:13 AM
> *To:* nmusers_at_globomaxnm.com
> *Subject:* RE: [NMusers] RE: Estimation of ke0 from raw data
>
> Semicompartmental method is implemented in WinNonlin Phoenix and sites
> Kowalski and Karim (1995), A semicompartmental modeling approach for
> pharmacodynamic data assessment, J Pharmacokinet Biopharm 23:307-22.
>
> *From:*owner-nmusers_at_globomaxnm.com
> <mailto:owner-nmusers_at_globomaxnm.com>
> [mailto:owner-nmusers_at_globomaxnm.com] *On Behalf Of *Bonate, Peter
> *Sent:* Saturday, September 05, 2015 5:40 PM
> *To:* Leonid Gibiansky
> *Cc:* Lommerse, JPM (Jos); Samer Mouksassi; nmusers_at_globomaxnm.com
> <mailto:nmusers_at_globomaxnm.com>
> *Subject:* Re: [NMusers] RE: Estimation of ke0 from raw data
>
> Ken Kowalski published a paper many years ago which I think he called
> a semicompartmental method. It was not developed as a population
> approach and only applies to single dose data but works really well
> under those conditions. It was published in the Journal of
> Pharmacokinetics and Biopharmaceutics.
>
> Pete Bonate.
>
>
>
> > On Sep 5, 2015, at 4:37 PM, Leonid Gibiansky
> <lgibiansky_at_quantpharm.com <mailto:lgibiansky_at_quantpharm.com>> wrote:
> >
> > Jos,
> >
> > It is not very clear what exactly you need. If you can use modeling
> tools, then linear interpolation + effect compartment + Emax model for
> the effect compartment versus PD dependence should work. If you would
> like to use only the raw data, no modeling, NCA style analysis, then
> the difference between Tmax of PK and Tmax of PD could be used as a
> crude estimate of the delay. Or you can use hysteresis curve for the
> PK curve with the time delay (with linear interpolation) and PD, and
> change the time delay for PK part until the hysteresis would disappear
> (using some metrics what does it mean "disappear"; may be area inside
> the loop is small). The time shift that provides smallest hysteresis
> area is the delay time.
> >
> > Leonid
> >
> >
> >
> > --------------------------------------
> > Leonid Gibiansky, Ph.D.
> > President, QuantPharm LLC
> > web: www.quantpharm.com <http://www.quantpharm.com>
> > e-mail: LGibiansky at quantpharm.com <http://quantpharm.com>
> > tel: (301) 767 5566
> >
> >
> >
> >> On 9/5/2015 2:44 PM, Lommerse, JPM (Jos) wrote:
> >> Dear Samer,
> >>
> >> Thank you for the reference.
> >>
> >> However, the method of Fuseau assumes
> >>
> >> that a mathematical description for
> >>
> >> the PK curve is available.
> >>
> >> I would like to do without such a PK description
> >>
> >> and directly use the PK observations, e.g. applying
> >>
> >> linear interpolation between the PK data points.
> >>
> >> Would that be feasible?
> >>
> >> Thanks, Jos
> >>
> >> *From:*Samer Mouksassi [mailto:Samer.Mouksassi_at_certara.com]
> >> *Sent:* Saturday, September 05, 2015 8:34 PM
> >> *To:* Lommerse, JPM (Jos); nmusers_at_globomaxnm.com
> <mailto:nmusers_at_globomaxnm.com>
> >> *Subject:* RE: Estimation of ke0 from raw data
> >>
> >> Dear Jos,
> >>
> >> Please have a look at the algorithm detailed in the appendix of this
> >> publication:
> >>
> >> Fuseau E, Sheiner LB.
> >>
> >> Simultaneous modeling of pharmacokinetics and pharmacodynamics with a
> >> nonparametric pharmacodynamic model.
> >>
> >> Clin Pharmacol Ther. 1984 Jun;35(6):733-41.
> >>
> >> Regards,
> >>
> >> Samer
> >>
> >> *From:* owner-nmusers_at_globomaxnm.com
> <mailto:owner-nmusers_at_globomaxnm.com>
> >> <mailto:owner-nmusers_at_globomaxnm.com>
> >> [mailto:owner-nmusers_at_globomaxnm.com] *On Behalf Of *Lommerse, JPM
> (Jos)
> >> *Sent:* Saturday, September 5, 2015 1:44 PM
> >> *To:* nmusers_at_globomaxnm.com <mailto:nmusers_at_globomaxnm.com>
> <mailto:nmusers_at_globomaxnm.com>
> >> *Subject:* [NMusers] Estimation of ke0 from raw data
> >>
> >> Hi,
> >>
> >> I have a data set containing PK concentrations and PD effect.
> >>
> >> When plotting PD as a function of PD a clear anti-clockwise hysteresis
> >>
> >> plot appears.
> >>
> >> I would like to get a (rough) estimate of the PD time delay w.r.t. the
> >> PK without
> >>
> >> using a compartmental description for the observed PK, even not using
> >>
> >> a polynomal function that fits the PK. The assumption I make is that
> >>
> >> all PD delay can be explained by the delay through an effect
> compartment.
> >>
> >> I am wondering if methods exist that solely use the raw data to
> >>
> >> calculate such time delays.
> >>
> >> Thank you for any comment/suggestion,
> >>
> >> Jos
> >>
> >> *Jos Lommerse*
> >>
> >> Modeler Consultant
> >>
> >> /Quantitative Solutions BV/
> >>
> >> /Molenweg 79/
> >>
> >> /5349 AC Oss/
> >>
> >> /The Netherlands/
> >>
> >> jlommerse_at_wequantify.com <mailto:jlommerse_at_wequantify.com>
> <mailto:jlommerse_at_wequantify.com>
> >>
> >> +31 412 211102
> >>
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Received on Mon Sep 14 2015 - 14:49:34 EDT

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