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RE: RE: Estimation of ke0 from raw data

From: Lommerse, JPM <jos.lommerse>
Date: Tue, 8 Sep 2015 15:38:01 +0200

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 xnm.com [mailto:owner-nmusers
Sent: Sunday, September 06, 2015 12:13 AM
To: nmusers
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 ilto:owner-nmusers
Sent: Saturday, September 05, 2015 5:40 PM
To: Leonid Gibiansky
Cc: Lommerse, JPM (Jos); Samer Mouksassi; nmusers
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
>
> 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
>> *Sent:* Saturday, September 05, 2015 8:34 PM
>> *To:* Lommerse, JPM (Jos); nmusers om<mailto:nmusers
>> *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
>> <mailto:owner-nmusers
>> [mailto:owner-nmusers
>> *Sent:* Saturday, September 5, 2015 1:44 PM
>> *To:* nmusers
>> *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 mmerse
>>
>> +31 412 211102
>>
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