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

From: Bonate, Peter <Peter.Bonate_at_astellas.com>
Date: Sat, 5 Sep 2015 21:40:29 +0000

Ken Kowalski published a paper many years ago which I think he called a sem=
icompartmental method. It was not developed as a population approach and on=
ly applies to single dose data but works really well under those conditions=
. It was published in the Journal of Pharmacokinetics and Biopharmaceutic=
s.

Pete Bonate.



> On Sep 5, 2015, at 4:37 PM, Leonid Gibiansky <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 effec=
t compartment versus PD dependence should work. If you would like to use on=
ly the raw data, no modeling, NCA style analysis, then the difference betwe=
en 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 (wit=
h linear interpolation) and PD, and change the time delay for PK part until=
 the hysteresis would disappear (using some metrics what does it mean "disa=
ppear"; 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 - 17:40:29 EDT

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