Imph
★    

2023-06-27 15:06
(384 d 15:35 ago)

Posting: # 23621
Views: 2,067
 

 concentration-time profile with two peaks or more [NCA / SHAM]

Hi,
can you scp enlighten me on how to choose the Cmax in the presence of a profile with two peaks or more?
Thank you in advance.
dshah
★★  

India/United Kingdom,
2023-06-27 15:13
(384 d 15:28 ago)

@ Imph
Posting: # 23622
Views: 1,785
 

 concentration-time profile with two peaks or more

Hi ImpH!
Cmax is defined as highest concentration obtained after dose irrespective of number of peaks. The peaks can be observed due to various reason like enterohepatic recirculation and many more.
Regards,
Divyen
Imph
★    

2023-06-27 15:26
(384 d 15:15 ago)

@ dshah
Posting: # 23623
Views: 1,769
 

 concentration-time profile with two peaks or more

❝ Cmax is defined as highest concentration obtained after dose irrespective of number of peaks. The peaks can be observed due to various reason like enterohepatic recirculation and many more.


Thank you for you quick response. So I have to choose the peak showing the highest concentration among the two?
Helmut
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2023-06-27 15:44
(384 d 14:58 ago)

@ Imph
Posting: # 23625
Views: 1,812
 

 What does ‘max’ in Cmax mean?

Hi Imph,

❝ ❝ Cmax is defined as highest concentration obtained after dose irrespective of number of peaks. The peaks can be observed due to various reason like enterohepatic recirculation and many more.


❝ […] So I have to choose the peak showing the highest concentration among the two?


Read what Divyen stated above again. By definiton the highest concentration! :-D

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Imph
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2023-06-27 17:18
(384 d 13:24 ago)

@ Helmut
Posting: # 23626
Views: 1,757
 

 What does ‘max’ in Cmax mean?

❝ ❝ […] So I have to choose the peak showing the highest concentration among the two?


❝ Read what Divyen stated above again. By definiton the highest concentration! :-D


yes logically, the issue is that I have read that some softwares systematically take the first peak to define the cmax.
Helmut
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2023-06-27 17:24
(384 d 13:18 ago)

@ Imph
Posting: # 23627
Views: 1,761
 

 Which software?

Hi Imph,

❝ ❝ Read what Divyen stated above again. By definiton the highest concentration! :-D


❝ yes logically, the issue is that I have read that some softwares systematically take the first peak to define the cmax.


Which one? I’ve tested 17 (both commercial an open-source). Would be crazy!

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Imph
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2023-06-27 18:56
(384 d 11:45 ago)

@ Helmut
Posting: # 23628
Views: 1,737
 

 Which software?

Hi,

In the WinNonlin guide, this is how tmax is defined:

Tmax: Time of maximum observed concentration. For non-steady-state data, the entire curve is considered. If the maximum observed concentration is not unique, then the first maximum is used
Helmut
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2023-06-27 19:03
(384 d 11:39 ago)

@ Imph
Posting: # 23629
Views: 1,747
 

 tmax ≠ Cmax 🙂

Hi Imph,

❝ In the WinNonlin guide, this is how tmax is defined:


❝ Tmax: Time of maximum observed concentration. For non-steady-state data, the entire curve is considered. If the maximum observed concentration is not unique, then the first maximum is used


Sure, but you were talking about Cmax – not tmax. That’s how it is implemented in all software I know.
During a training a smart-ass said “That’s all wrong! If there are identical maxima, tmax should be reported as the median of observed times.” I think that’s a rather academic question. How likely is it to have exactly (‼) the same concentrations?

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Imph
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2023-06-27 19:33
(384 d 11:08 ago)

@ Helmut
Posting: # 23630
Views: 1,802
 

 tmax ≠ Cmax 🙂

❝ ❝ Tmax: Time of maximum observed concentration. For non-steady-state data, the entire curve is considered. If the maximum observed concentration is not unique, then the first maximum is used


❝ Sure, but you were talking about Cmax – not tmax. That’s how it is implemented in all software I know.


Yes but the Cmax was defined accordingly:

Cmax: Maximum observed concentration, occurring at time Tmax, as defined above.

When reading this, we can easily think that the software would take the first peak as Cmax.


Edit: Full quote removed. Please delete everything from the text of the original poster which is not necessary in understanding your answer; see also this post #5[Helmut]
BEQool
★    

2023-06-27 20:25
(384 d 10:17 ago)

@ Imph
Posting: # 23631
Views: 1,717
 

 tmax ≠ Cmax 🙂

❝ ❝ ❝ Tmax: Time of maximum observed concentration. For non-steady-state data, the entire curve is considered. If the maximum observed concentration is not unique, then the first maximum is used


❝ Yes but the Cmax was defined accordingly:


❝ Cmax: Maximum observed concentration, occurring at time Tmax, as defined above.


❝ When reading this, we can easily think that the software would take the first peak as Cmax.


Hello Imph,

if I am not mistaken, I think that you may be mixing peaks with maximums (maximum ≠ peak)?
You may have multiple peaks in a profile but normally (almost always) just one maximum concentration and this one maximum concentration defines Tmax.
Just in extreme rare cases when you have two identical maximum concentrations (not just two peaks but two peaks with the same highest concentration) at different sampling time points, the software (WinNonlin) uses first highest concentration (Cmax) sampling point as Tmax.
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