Log in
Register|
msmnainar ★ India, 2015-02-16 14:41 (3735 d 23:19 ago) Posting: # 14429 Views: 16,045 |
|
|
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 (3735 d 23:14 ago) @ msmnainar Posting: # 14430 Views: 14,748 |
|
|
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 (3735 d 23:09 ago) @ ElMaestro Posting: # 14431 Views: 14,760 |
|
|
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 (3735 d 22:58 ago) @ msmnainar Posting: # 14432 Views: 14,787 |
|
|
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 (3735 d 22:37 ago) @ ElMaestro Posting: # 14433 Views: 14,771 |
|
|
Jo is heid scho wiada Weihnachten?  — Kindest regards, nobody |
|
Dr_Dan ★★ Germany, 2015-02-17 09:11 (3735 d 04:49 ago) @ ElMaestro Posting: # 14434 Views: 14,633 |
|
|
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 (3735 d 03:21 ago) @ Dr_Dan Posting: # 14435 Views: 14,631 |
|
|
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 (3735 d 02:18 ago) @ nobody Posting: # 14436 Views: 14,605 |
|
|
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) CmaxCmax = 100 ng/ml AUC = 38.3 ng·h/ml Have a nice day! Jan |
|
nobody nothing 2015-02-17 12:19 (3735 d 01:41 ago) @ janmacek Posting: # 14437 Views: 14,631 |
|
|
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 (3735 d 01:23 ago) @ nobody Posting: # 14438 Views: 14,547 |
|
|
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 (3734 d 22:04 ago) @ janmacek Posting: # 14439 Views: 14,632 |
|
|
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 (3734 d 20:57 ago) @ ElMaestro Posting: # 14440 Views: 14,548 |
|
|
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 (3734 d 20:28 ago) @ janmacek Posting: # 14441 Views: 14,589 |
|
|
Hi again! Sorry, but before we end up in the flame board 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 ★★★   Vienna, Austria, 2015-02-17 18:06 (3734 d 19:54 ago) @ janmacek Posting: # 14442 Views: 14,671 |
|
|
Dear Jan, ❝ […] the discussion was simply about comparison of two numbers, 1000 and 730. ![[image]](img/uploaded/image281.png) 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]](https://static.bebac.at/pics/Blue_and_yellow_ribbon_UA.png) Helmut Schütz ![[image]](https://static.bebac.at/img/CC by.png) 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 (3734 d 19:17 ago) @ Helmut Posting: # 14443 Views: 14,531 |
|
|
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 (3734 d 18:07 ago) @ Dr_Dan Posting: # 14444 Views: 14,508 |
|
|
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 (3734 d 16:43 ago) @ Dr_Dan Posting: # 14448 Views: 14,481 |
|
|
...noch is Fasching — Kindest regards, nobody |
Ing. Helmut Schütz