anky1212
☆    

India,
2016-12-27 15:50
(2649 d 00:01 ago)

Posting: # 16884
Views: 5,558
 

 AntiemeticDrug selection for BE study of Carbidopa, Levodopa and Entacapone [PK / PD]

Hi all,

Can anyone suggest which antiemetic shall be used to mitigate undesirable effect of Carbidopa, Levodopa and Entacapone tablets like nausea, vomiting in Bioequivalence study in normal human subjects?

Please share antiemetic drug with reference.

Thanks and regards,
Anky
BE-proff
●    

2016-12-27 16:08
(2648 d 23:43 ago)

@ anky1212
Posting: # 16885
Views: 4,839
 

 AntiemeticDrug selection for BE study of Carbidopa, Levodopa and Entacapone

Hi anky1212,

I can see two options:
  1. if you are sure that healthy volunteers are ethically acceptable you could randomize more people to cover possible dropouts due to vomiting
  2. to utilize patients
anky1212
☆    

India,
2016-12-27 16:43
(2648 d 23:08 ago)

@ BE-proff
Posting: # 16886
Views: 4,825
 

 AntiemeticDrug selection for BE study of Carbidopa, Levodopa and Entacapone

❝ I can see two options:

  1. if you are sure that healthy volunteers are ethically acceptable you could randomize more people to cover possible dropouts due to vomiting

  2. to utilize patients

Thanks for reply.

We are planning to enroll healthy human volunteer. My only concern is to use appropriate antiemetic drug which was used previously in trial/ BE study of LCE.

Please suggest appropriately.

Thanks
mittyri
★★  

Russia,
2016-12-27 18:15
(2648 d 21:36 ago)

@ anky1212
Posting: # 16887
Views: 4,851
 

 Antiemetic Drugs can change PK profiles

Dear anky1212,

This question is not so easy to answer.
The best way to control vomiting and nausea is peripheral dopamine receptor blocker like Domperidone or central blocker like Metoclopramide (also blocks central effects, but they aren't needed here, right?).
By the way using these drugs you can change gastric/enteric motility and also bioavailability of drugs of interest.
Please consider to review this paper
I didn't find any data regarding active antiemetic therapy in BEQ studies for Stalevo.

Maybe more experienced colleagues have more information...

Kind regards,
Mittyri
anky1212
☆    

India,
2016-12-27 19:02
(2648 d 20:49 ago)

@ mittyri
Posting: # 16888
Views: 4,862
 

 Antiemetic Drugs can change PK profiles

Thanks mittyri for your reply.

Since domperidone increases bioavailability, we may not use it for BE of LCE. Also, drugs which is dopamine antagonist may worsen pd symptoms and may not be used as antiemetic for BE OF LCE.

Can we use ondansetron for BE of LCE to mitigate emesis, nausea?

But i need reference for the same which i couldn't fimd.

Please reply if anyone finds reference or any useful suggestion.


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]
mittyri
★★  

Russia,
2016-12-27 20:33
(2648 d 19:18 ago)

@ anky1212
Posting: # 16890
Views: 4,892
 

 Antiemetic Drugs can change PK profiles

Dear anky1212,

❝ Also, drugs which is dopamine antagonist may worsen pd symptoms and may not be used as antiemetic for BE OF LCE.


We are trying to prevent the dopamine-induced AE, right? Your subjects will be healthy, I suppose no PD in anamnesis. Due to the antagonism dopamine blockers are No1. I think metoclopramide would be even more effective due to the central effect, but not sure.

❝ Can we use ondansetron for BE of LCE to mitigate emesis, nausea?


Yes, you can, but it would be not so effective as dopamine blockers.

❝ But i need reference for the same which i couldn't fimd.


I think no one performed such a study (LCE/LCE+Ondansetron) due to lack of physiological basis of interaction.
BTW ondansetron is mentioned as an antiemetic treatment in PD here and here

Kind regards,
Mittyri
luvblooms
★★  

India,
2016-12-28 09:05
(2648 d 06:46 ago)

@ anky1212
Posting: # 16891
Views: 4,850
 

 AntiemeticDrug selection for BE study of Carbidopa, Levodopa and Entacapone

Hi Anky


❝ Can anyone suggest which antiemetic shall be used to mitigate undesirable effect of Carbidopa, Levodopa and Entacapone tablets like nausea, vomiting in Bioequivalence study in normal human subjects?


Not for the said combination but yes, many companies have used antiemetic drugs to counteract the nausea and vomiting observed with certain anticholinesterases.

Details available at A Randomized, Crossover, Single-Dose Bioequivalence Study of Two Extended-Release Tablets of Donepezil 23 mg in Healthy Human Volunteers under Fasting and Fed States


And product was approved by USFDA


❝ Please share antiemetic drug with reference.




My suggestion, write to FDA before starting any study if you are doubtful.

~A happy Soul~
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