Bioequivalence and Bioavailability Forum • Difference between Cminss and Ctauss?

tekwani.sunil
☆

India,
2014-12-03 08:10
(3425 d 07:43 ago)

Posting: # 13970
Views: 6,090

Difference between Cminss and Ctauss? [NCA / SHAM]

Please help me with the definitions of Ctau and Cmin at steady state.

According to EMEA BE guideline for MR products: Ctauss is Concentration at the end of the dosing interval at steady state

and

Cminss: Minimum plasma concentration at steady state.

Please explain me in details the difference. And why the values of Ctauss are higher than Cminss?

At which point in the Steady state P'kinetics graph do we measure both of them?

Edit: Category changed. [Helmut]

Helmut ★★★ Vienna, Austria, 2014-12-03 14:11 (3425 d 01:42 ago) @ tekwani.sunil Posting: # 13972 Views: 5,219	Difference between Cminss and Ctauss? Post reply
	Hi Tekwani, see http://bebac.at/lectures/Prague2013WS3.pdf. — Dif-tor heh smusma 🖖🏼 Довге життя Україна! Helmut Schütz The quality of responses received is directly proportional to the quality of the question asked. 🚮 Science Quotes

tekwani.sunil ☆ India, 2014-12-04 06:53 (3424 d 09:00 ago) @ Helmut Posting: # 13975 Views: 5,176	Difference between Cminss and Ctauss? Post reply
	Thanks Helmut, Thanks for the help. If 90% confidence interval falls between 80-125% for only Cminss but not for Ctauss, what justification can be given? Can it be justified that the submission is done before the implementation of new MR guideline (which is effective from 1 June 2015), so 90% CI of Cminss should be considered?

Helmut
★★★

Vienna, Austria,
2014-12-04 15:21
(3424 d 00:32 ago)

@ tekwani.sunil
Posting: # 13977
Views: 5,069

Difference between Cminss and Ctauss?

Post reply

Hi Tekwani,

❝ If 90% confidence interval falls between 80-125% for only Cminss but not for Ctauss, what justification can be given?

You have to evaluate the study according to the protocol. But: EMA’s definition was given in the 2013 MR draft and already 2010 in the comments to the IR BE-GL (“By C_min,ss we mean the concentration at the end of the dosage interval”). Nothing really new.

❝ Can it be justified that the submission is done before the implementation of new MR guideline (which is effective from 1 June 2015), so 90% CI of Cminss should be considered?

That’s not a justification, but some organizational chitchat. Even if you claim that you were not aware of the new metric (and therefore, the study was not powered to show BE for it), you could try to scale the limits. See this post.

PS: In the past comments were published together with final guidelines. MR-GL? Nothing so far. :confused:

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes