RE: RE: Estimation of ke0 from raw data

From: [email protected] [mailto:[email protected]] On Behalf Of Bonate, Peter Sent: Saturday, September 05, 2015 5:40 PM To: Leonid Gibiansky Cc: Lommerse, JPM (Jos); Samer Mouksassi; [email protected] 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 > <[email protected]<mailto:[email protected]>> 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: http://www.quantpharm.com > e-mail: LGibiansky at 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:[email protected]] >> *Sent:* Saturday, September 05, 2015 8:34 PM >> *To:* Lommerse, JPM (Jos); >> [email protected]<mailto:[email protected]> >> *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:* [email protected]<mailto:[email protected]> >> <mailto:[email protected]> >> [mailto:[email protected]] *On Behalf Of *Lommerse, JPM (Jos) >> *Sent:* Saturday, September 5, 2015 1:44 PM >> *To:* [email protected]<mailto:[email protected]> >> <mailto:[email protected]> >> *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/ >> >> [email protected]<mailto:[email protected]> >> <mailto:[email protected]> >> >> +31 412 211102 >> >> Notice: This e-mail message, together with any attachments, contains >> information of Merck & Co., Inc. (2000 Galloping Hill Road, Kenilworth, >> New Jersey, USA 07033), and/or its affiliates Direct contact information >> for affiliates is available at >> http://www.merck.com/contact/contacts.html) >> that may be confidential, >> proprietary copyrighted and/or legally privileged. It is intended solely >> for the use of the individual or entity named on this message. 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