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

From: Leonid Gibiansky <lgibiansky_at_quantpharm.com>
Date: Sat, 5 Sep 2015 17:34:14 -0400

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
e-mail: LGibiansky at 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
> *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] *On Behalf Of *Lommerse, JPM (Jos)
> *Sent:* Saturday, September 5, 2015 1:44 PM
> *To:* 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>
>
> +31 412 211102
>
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Received on Sat Sep 05 2015 - 17:34:14 EDT

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