# PharmPK Discussion - Using Tmax as primary endpoint

PharmPK Discussion List Archive Index page
• On 19 Jun 2009 at 09:12:26, Paloma Blanca (pb3953.-a-.gmail.com) sent the message

Has anyone conducted a trial to compare two formulations where Tmax
was the primary parameter of interest? Any suggestions on how you
would calculate a sample size for a cross-over design using non-
parametric methods, if possible?

Thanks for your input.

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• On 19 Jun 2009 at 10:48:11, ganesh mugundu (ganesh.mugundu.-a-.gmail.com) sent the message

It would be interesting to know why Tmax would be a primary parameter
of interest rather than exposure and Cmax.

Ganesh Mugundu

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• On 19 Jun 2009 at 11:37:08, "Ed O'Connor" (Bioconsul09.at.cox.net) sent the message

The following message was posted to: PharmPK

It often becomes one especially where the collection times differ
between
the two formulations. As an aside I was asked to explain why our
bioanalytical results were so different. I found that the original
formulation was sampled at 5 minutes and the replacement at 10 minutes.

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• On 19 Jun 2009 at 12:58:04, William Wolowich (wwolowic.aaa.nova.edu) sent the message

The following message was posted to: PharmPK

In addition to the sampling time issue, Tmax is dependent on ka and ke:

Tmax= Ln(ka/ke) / ka-ke

And since ke is dependent on CL and V

Tmax = Ln(ka*V/CL) / ka - (CL/V)

William R. Wolowich, Pharm.D., R.Ph.
Chair and Assistant Professor
Department of Pharmacy Practice
College of Pharmacy
Nova Southeastern University
wwolowic.-a-.nsu.nova.edu

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• On 19 Jun 2009 at 19:38:27, Nick Holford (n.holford.-at-.auckland.ac.nz) sent the message

Hi,

This discussion clearly illustrates the silliness of describing a
continuous variable (time course of drug concentration) with extremely
design specific analysis methods (the time of the highest measured
conc).

If you really want to compare an estimate of the time of the highest
actual concentration then at least consider a method that allows
interpolation between the design specific sampling times.
Compartmental models would be the most obvious way to do the
interpolation but almost anything is better than using the times you
actually measured the concentrations!

Nick

--
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New
Zealand
n.holford.-a-.auckland.ac.nz
http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford

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• On 19 Jun 2009 at 22:43:20, "Zafar Iqbal , Prof Dept of Pharmacy UOP Iqbal" (zafar_iqbal.aaa.upesh.edu.pk) sent the message

it is better to use Cmax and AUC as a primary parameters
DR Zafar

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• On 21 Jun 2009 at 08:42:25, "Ed O'Connor" (Bioconsul09.-a-.cox.net) sent the message

The following message was posted to: PharmPK

Remember cMax is tied to tMax. They are compleltey dependent on the
precision and accuracy of sampling

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• On 22 Jun 2009 at 09:57:37, "Bruce Charles" (b.charles1.-a-.uq.edu.au) sent the message

The following message was posted to: PharmPK

More fundamentally the "quality" of information provided (or lack
thereof) depends on the actual sampling design.

Cheers
BC

Bruce CHARLES, BPharm (Hons), PhD, GradDipBusAdmin, MPS
School of Pharmacy
The University of Queensland,
Australia 4072

b.charles1.aaa.uq.edu.au
htpp://www.uq.edu.au/pharmacy/brucecharles/charles.html

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• On 21 Jun 2009 at 16:59:12, "Walt Woltosz" (walt.at.simulations-plus.com) sent the message

The following message was posted to: PharmPK

Ed,

Although Cmax is tied to Cmax in the sense that Tmax is when Cmax
occurs,
there can be great difficulty in establishing both when the plasma
concentration-time curve is relatively flat, as with some controlled
release
dosage forms. Then the sampling times become especially important in
order
to best capture when Cmax occurred. The catch is that for controlled
release
doses, sampling times are often more widely spaced, offering greater
opportunity for missing important data between them. There will be times
when one can only hope that either the data or a model will be
sufficient to
estimate what's going on between the observations.

Best regards,

Walt Woltosz
Chairman & CEO
Simulations Plus, Inc. (NASDAQ: SLP)
42505 10th Street West
Lancaster, CA 93534-7059
U.S.A.
http://www.simulations-plus.com
E-mail: walt.-a-.simulations-plus.com

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• On 22 Jun 2009 at 11:51:20, "Norris, Ross" (Ross.Norris.at.mater.org.au) sent the message

The following message was posted to: PharmPK

Bruce,

I assume this is in response to my question with respect to number and
timing of
samples for determination of AUC?

Regards,

Ross Norris,
PhD, MAppSc, BAppSc.
Research Consultant, Australian Centre for Paediatric Pharmacokinetics &
Therapeutic Advisory Service, Mater Pharmacy Services, Raymond Terrace,
South Brisbane, Q 4101, Australia.
Associate Professor, School of Pharmacy, Griffith University, Gold Coast
Qld Australia.
Senior Lecturer, School of Pharmacy, University of Queensland, St Lucia,
Qld Australia.

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• On 22 Jun 2009 at 11:26:37, David Foster (David.Foster.at.unisa.edu.au) sent the message

I agree Bruce,

I think that was Nick's point (which a few others seemed to have
missed?). Tmax and Cmax can be seriously affected by the (often
arbitrary!) sampling scheme, not to mention being difficult to use to
refine/inform future studies/trials. In contrast, actual modelling is
"less" affected.

Regards,

David

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• On 22 Jun 2009 at 10:03:08, "Ed O'Connor" (Bioconsul09.at.cox.net) sent the message

The following message was posted to: PharmPK

My point is that the logistics around establishing an accurate tMax
become
extremely taxing as you draw closer to the time of drug admin-
especially for
a dose going IV or IA.

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