msmnainar
★    

India,
2015-02-16 14:41
(3328 d 09:34 ago)

Posting: # 14429
Views: 13,890
 

 Cmax value higher than AUC [PK / PD]

Dear All

Is it possible to get Cmax value is higher than that of ACU value in a typical bioequivalence study? If yes, what are all those cases?

Thanks,

Sundar. M
ElMaestro
★★★

Denmark,
2015-02-16 14:46
(3328 d 09:29 ago)

@ msmnainar
Posting: # 14430
Views: 12,914
 

 Cmax value higher than AUC

Hi msnaimar,

❝ Is it possible to get Cmax value is higher than that of ACU value in a typical bioequivalence study? If yes, what are all those cases?


Cmax higher than AUC??? The two have different units and are not comparable - can you reformulate that question?

Pass or fail!
ElMaestro
msmnainar
★    

India,
2015-02-16 14:51
(3328 d 09:24 ago)

@ ElMaestro
Posting: # 14431
Views: 12,911
 

 Cmax value higher than AUC

Hi ElMaestro

For eg., obtained Cmax is 1000ng/mL and AUCt is 730ng8h/mL. I suspect this particular observations may due to data set error. However, I don't have raw data to verify this results, thus need expertise opinion.

Thanks

Sundar. M
ElMaestro
★★★

Denmark,
2015-02-16 15:01
(3328 d 09:13 ago)

@ msmnainar
Posting: # 14432
Views: 12,933
 

 Cmax value higher than AUC

Hi msnaimar,

❝ For eg., obtained Cmax is 1000ng/mL and AUCt is 730ng8h/mL. I suspect this particular observations may due to data set error. However, I don't have raw data to verify this results, thus need expertise opinion.


It doesn't make sense. At least not to me.
AUCt is a concentration integrated over time, Cmax is a concentration.

John has two shirts. One is green, the other one cost him $80. Which one is warmer?

Pass or fail!
ElMaestro
nobody
nothing

2015-02-16 15:23
(3328 d 08:52 ago)

@ ElMaestro
Posting: # 14433
Views: 12,910
 

 Cmax value higher than AUC

Jo is heid scho wiada Weihnachten? :-D

Kindest regards, nobody
Dr_Dan
★★  

Germany,
2015-02-17 09:11
(3327 d 15:04 ago)

@ ElMaestro
Posting: # 14434
Views: 12,777
 

 Cmax value higher than AUC

Hi ElMaestro

❝ It doesn't make sense. At least not to me.

❝ AUCt is a concentration integrated over time, Cmax is a concentration.


You are right that msnaimar can not directly compare two different units on the one hand but on the other hand the question is reasonable. Is it possible that Cmax > AUCt? IMHO not. Cmax just represents one point of the curve (o.k. it is the highest) but AUC represents all points under the curve i.e. Cmax + all the rest and therefore the value for AUC must be >> as the value for Cmax provided that you use the same dimension for concentration (in our case ng/ml), right?
Please explain if I am completely wrong
Kind regards
Dr_Dan

Kind regards and have a nice day
Dr_Dan
nobody
nothing

2015-02-17 10:38
(3327 d 13:36 ago)

@ Dr_Dan
Posting: # 14435
Views: 12,784
 

 Cmax value higher than AUC

Hi!

What would happen if...

- you apply an i.v. bolus of a compound with a half-life of 5 minutes
- calculate AUC as ng/ml h ?

Kindest regards, nobody
janmacek
☆    

Czech Republic,
2015-02-17 11:41
(3327 d 12:33 ago)

@ nobody
Posting: # 14436
Views: 12,760
 

 Cmax value higher than AUC

Hi nobody and Dr_Dan,

i.v. bolus is not typically administered in a bioequivalence study. But if we want to compare numerically AUC (ng.h/ml) and Cmax (ng/ml), it is possible that Cmax > AUC if the kinetics after oral administration is rapid (like in prodrugs).

Consider the following example

Time (h)   Cmax
0.000        0
0.167        2
0.333      100
0.500       50
0.750       25
1.000       12.5
1.250        4
1.500        1
1.750        0

Cmax = 100 ng/ml
AUC = 38.3 ng·h/ml

Have a nice day!

Jan
nobody
nothing

2015-02-17 12:19
(3327 d 11:56 ago)

@ janmacek
Posting: # 14437
Views: 12,757
 

 Cmax value higher than AUC

Hi jan!

PK is more than just this bioequi-thing ;-)

...and as you see, it works with absorption or without, but my example is really bare-metal :-)

Kindest regards, nobody
msmnainar
★    

India,
2015-02-17 12:36
(3327 d 11:38 ago)

@ nobody
Posting: # 14438
Views: 12,681
 

 Cmax value higher than AUC

Hi nobody

I totally agree with janmacek comment, since the drugs is pro-drug and its administered p.o.

Thanks

Sundar. M
ElMaestro
★★★

Denmark,
2015-02-17 15:56
(3327 d 08:19 ago)

@ janmacek
Posting: # 14439
Views: 12,783
 

 Magic ElMaestrolophystic Road­Show

Dear all,

highly distinguished respectable scientists of great reputation,

can we please, please reconnect with the real world?

❝ Cmax = 100 ng/ml

❝ AUC = 38.3 ng·h/ml


So AUC<Cmax?

Ladies and gentlemen, I give you:

The Magic ElMaestrolophystic RoadShow.
Coming to a town near you! Starring a handsome Dataset, a magic wand, and an SI unit.

We have AUC<Cmax where
AUC = 38.3 ng*hrs/mL

Let's see... How about converting time to SI units? One hour is 3600 seconds, so
AUC = 38.3 hrs * (3600 s/hrs)ng/mL

*drum roll*
*drum roll*
*drum roll*
*drum roll*
*drum roll*
*drum roll*
*drum roll*


=138*103 ng*s/mL
And we hence conclude that AUC>Cmax.
The Magic ElMaestrolophystic RoadShow has hereby shown that when AUC<Cmax then we can conclude that AUC>Cmax. Hocus Pocus. It is nothing less than black magic....




























....and a teeny-tiny dose of complete utter nonsense.

Pass or fail!
ElMaestro
janmacek
☆    

Czech Republic,
2015-02-17 17:02
(3327 d 07:12 ago)

@ ElMaestro
Posting: # 14440
Views: 12,709
 

 Magic ElMaestrolophystic Road­Show

Dear ElMaestro,

thank you for your reply in vivid colors, but your irony was exaggerated. We are all aware of the different units of Cmax and AUC and the discussion was simply about comparison of two numbers, 1000 and 730.

If you have 2 meters long rod and 1 liter large flask, can you compare the numbers two and one? Why not? The number 2 > 1 (numerical comparison), but, of course, it cannot be stated whether the rod is longer than the flask or the flask more voluminous than the rod.

I have stated clearly in my previous post that we are comparing AUC and Cmax numerically with respect to the given units.

By the way, the value of Cmax (ng/ml) will be > value of AUC(ng.h/ml) if

Cmax / tlast > Cavg = AUC(0-tlast)/tlast

With kind regards,

Jan
nobody
nothing

2015-02-17 17:32
(3327 d 06:43 ago)

@ janmacek
Posting: # 14441
Views: 12,675
 

 Magic ElMaestrolophystic Road­Show

Hi again!

Sorry, but before we end up in the flame board :-D

This AUC > Cmax is a rule of numb. Or maybe rule of dumb, but has nothing to do with science. Best I can imagine: Marketing. Or something like that.

AUC < Cmax will always apply, as long as I choose the timescale long enough (hours, days, weeks,...) for AUC compared to the terminal half-life of the compound. So this all is utter nonsense, as Maestro pointed out. You can not compare apples and bananas and come up with: apples are sweeter than bananas. Beyond kindergarten...

Kindest regards, nobody
Helmut
★★★
avatar
Homepage
Vienna, Austria,
2015-02-17 18:06
(3327 d 06:09 ago)

@ janmacek
Posting: # 14442
Views: 12,804
 

 Bizarre discussion…

Dear Jan,

❝ […] the discussion was simply about comparison of two numbers, 1000 and 730.


[image]OK, but is such a comparison meaningful at all? No way. We have values, which consist of two parts: a number and a unit.
IMHO, comparing numbers whilst ignoring units doesn’t make any [sic] sense.
Some physicians notoriously “forget” units. When they tell me “The patient has a value of 37!” I use to reply “37 what? Cats? That’s a lot if he lives in a small apartment.”

There is a nice thing in physics called unit equa­tion. Let’s go back to msmnainar’s example of Cmax 1,000 ng/mL and AUC 730 h×ng/mL. What do we mean in com­mon language when we say sum­fink is smaller than another? We calculate a dif­fe­rence (two apples are less than three) or a ratio (hey, T/R). In the former case the unit equation would no work at all and in the latter the result for AUC/Cmax would be 0.73 h. Gimme a break! Please don’t tell me that two apples are less than three oranges.

Another example: The orthodromic distance from Moscow to Vladi­vostoc is 6,434 km. Makes quite a walk. If we switch units – do you think that 0.0000000002085pc are shorter?

Dif-tor heh smusma 🖖🏼 Довге життя Україна! [image]
Helmut Schütz
[image]

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

Czech Republic,
2015-02-17 18:42
(3327 d 05:32 ago)

@ Helmut
Posting: # 14443
Views: 12,640
 

 Bizarre discussion…

Dear Helmut,

this is (and was) totally clear to me. But was that comparison not meaningful at all? I have correctly guessed that the drug was a pro-drug, so this is the additional information yielded from this comparison. And msnaimar (and we all) has the experience from previous studies that in the vast majority of cases the value of AUC > value of Cmax with the units specified, so he/she suspected an error.

I also always check the aberrant results (aberrant from other values obtained in the same experiment or aberrant from other studies), so it was correct that msnaimar asked his question. The ratio Cmax/AUC > 1 (with the units specified) says something about the shape and width of the concentration-time curve, i.e. the curve is sharpe and narrow.

Of course, if we would have also the values of tmax and t1/2 we could say more about the shape of the PK curve, but you can make some conclusions based only on Cmax and AUC.

With kind regards,

Jan
Dr_Dan
★★  

Germany,
2015-02-17 19:53
(3327 d 04:22 ago)

@ Dr_Dan
Posting: # 14444
Views: 12,653
 

 Cmax value higher than AUC

Hi
Cmax is missing the dimension time which is needed to compare the absolute value to AUC. So you need a third variable to link AUC and Cmax. This could be t1/2.

something like:
If AUCt with t > 5*t1/2 and t1/2 > 1.5 h then AUCt>Cmax

Can anybody calculate the threshold value for t1/2? 1.5 h was just a guess.

Kind regards
Dr_Dan

Kind regards and have a nice day
Dr_Dan
nobody
nothing

2015-02-17 21:16
(3327 d 02:58 ago)

@ Dr_Dan
Posting: # 14448
Views: 12,614
 

 Cmax value higher than AUC

...noch is Fasching :-D

Kindest regards, nobody
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