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chidambarajoshi ★ Hyderabad-INDIA, 2008-11-05 12:40 (6033 d 11:26 ago) Posting: # 2631 Views: 9,866 |
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Dear all, We have conducted a study on Finasteride, and the literature reported value for Cmax of Reference Proscar is 27-49 ng/mL, but we have got 58 ng/mL. What is impact on the study? But ultimately testproduct was found to be Bioequivalent. Thanks, Joshi |
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ElMaestro ★★★ Denmark, 2008-11-05 12:56 (6033 d 11:10 ago) @ chidambarajoshi Posting: # 2632 Views: 8,324 |
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Hi Joshi, Check the data in the literature: Was the study (where the reference values were found) conducted in the US, Europe or similar area with a high population of fat bums? Bearing in mind that such populations have very high body masses (body volumes, plasma volumes, Vd's, blahblah) you would expect to see a difference to a study carried out in a population of people that are lighter/smaller, such as in India or China. If you are lucky you can even find average (median) body masses etc of the 'reference' population which you can compare to your own. At any rate, this should not have a negative impact on your conclusion or the evaluation. If one the other hand you have carried out the study in a population that is very similar to that used in the literature (and if environmental factors too are similar [food etc]) then a regulator might wonder. EM. |
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chidambarajoshi ★ Hyderabad-INDIA, 2008-11-06 11:07 (6032 d 13:00 ago) @ ElMaestro Posting: # 2636 Views: 8,309 |
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Dear EM, Yeh! I have checked all you have listed data only reveals that the age group >50 years are showing maximum absoption up to 58 ng and AUC >320. But the normal BMI study results are absolutely complying with the repoted value of 27-49 ng/mL. And for Proscar no racial studies are conducted. Finasteride is metabolised with 3A4 CYP, whose % is almost equal in all races, Please help...! Regards — Best Regards Joshi |
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ElMaestro ★★★ Denmark, 2008-11-06 14:04 (6032 d 10:02 ago) @ chidambarajoshi Posting: # 2637 Views: 8,306 |
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Hi again, this might not be too much of a problem. If I get you right -I am not sure I do, sorry- then you cannot see a BW difference between your population and the population for which the ref values were found. At any rate, you are only comparing two products now, and as you said they are bioequivalent. If there's something 'wrong' with your product then there's also something wrong with the originator's product, right? That's simply not something an assessor is able to judge in a straightforward fashion. Liver metabolism can certainly be tricky. For example, the hepatic blood flow is depending on the posture; the rate of metabolism will therefore potentially differ between people who sit, stand and lye down (did your volunteers sit, stand, walk as much as the volunteers in the ref study did`, etc etc). Finally, please tell about your patients (BW, race, diet) and please tell what you know about the patients in the ref study. EM |
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chidambarajoshi ★ Hyderabad-INDIA, 2008-11-10 09:00 (6028 d 15:06 ago) @ ElMaestro Posting: # 2644 Views: 8,218 |
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Hi EM! Thanks for the reply ❝ If there's something 'wrong' with your product then there's also something ❝ wrong with the originator's product, right? That's simply not something an ❝ assessor is able to judge in a straightforward fashion.  Okay! Regarding subject's data This study was conducted in subjects of BW ranging from 51 kg to 85 kg ie., normal Body mass index between 18.5 kg/m2 to 24.9 kg/m2. Age is between 18-45 years and race is Asian (India). And the subjects left at sitting posture for 2hr post dose and after 2hrs they allowed do nomal activities but no too much physical exertion. Regards, Joshi -- Edit: original quotes restored. [Helmut] — Best Regards Joshi |
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ElMaestro ★★★ Denmark, 2008-11-13 15:08 (6025 d 08:59 ago) @ chidambarajoshi Posting: # 2664 Views: 8,204 |
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Hi again, I am sorry if I failed to make myself clear. In a BE-study the rate and extent of absorption is compared across two formulations. What is not tested -and most often not evaluated- is if the observed values are reasonable. From the assessor's side, things can be overwhelmingly complicated, because the trial is not designed to characterise the PK of each formulation per se, but to compare two simple aspects of their PK. Thus, an assessor has very little to do if a surprising value is observed. A good example is if clearance varies between two periods. That could give rise to a significant period effect, but an assessor would think "carry-over" etc because equal clearance is an untested assumption of a good BE trial. It is totally obscure. Here we have a situation where you compare across two studies that have been performed 5 or 10 years (or whatever) apart, with different people of different race/ethinicity, and so forth. I don't think the comparison needs to be very strict. Whether or not one should wonder if there were a x2, x5 or x10 difference I cannot tell. But x2 is in my subjective and unqualified opionion not something that necessarily makes the alarm go off. In case the alarm goes off an assessor can ask for an inspection, but then there should be a really good reason, imho. The chance is high that nothing is found, I guess (without knowing). It might be you forgot a factor 2 dilution or something during the evaluation. Even if this were the case it would still not be a problem per se. You give some facts here about your own study, but please give the facts ytou know about the reference study. That might help shed further light over your observation. EM. |
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Helmut ★★★   Vienna, Austria, 2008-11-13 15:24 (6025 d 08:43 ago) @ ElMaestro Posting: # 2666 Views: 8,382 |
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Dear ElMaestro and Joshi, I agree to 100% with ElMaestro. If we gueestimate the mean Cmax from the reference study with sqrt(27x49) = 36.4ng/mL, the results of Joshi's study (58ng/mL) are just 59% higher; nothing which would really bother me in an inter-study comparison. — 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 |
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chidambarajoshi ★ Hyderabad-INDIA, 2008-11-17 12:00 (6021 d 12:06 ago) @ ElMaestro Posting: # 2683 Views: 8,106 |
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Hi EM! Thanks for the detailed reply ❝ You give some facts here about your own study, but please give the facts ❝ ytou know about the reference study. That might help shed further light ❝ over your observation. I did the same and I had given some reference reports to regulators where the Cmax has reached 49ng/mL and AUC up to 350. Crossing my finger and waiting for accessor's Reply Thanks Joshi — Best Regards Joshi |
Ing. Helmut Schütz