NK
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India,
2024-01-19 05:24
(44 d 21:28 ago)

Posting: # 23832
Views: 926
 

 Steady state BE study dosing [Design Issues]

Dear All,

We are planning a steady state bioequivalence study on healthy subject with tid dosing (every 8 hours) on day 1 to day 4. Serial PK blood sample collections are planned on Day 5 after morning dosing(expected to reach steady state concentration on day 5).

Kindly clarify, whether 2nd and 3rd dose on day 5 need to be administered or not? and sampling should be continued for 24 hours?

Thanks in advance!

Regards
NK


Edit: Category changed; see also this post #1[Helmut]
Helmut
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Vienna, Austria,
2024-01-20 13:50
(43 d 13:01 ago)

@ NK
Posting: # 23834
Views: 824
 

 Circadian rhythm?

Hi NK,

❝ We are planning a steady state bioequivalence study on healthy subject with tid dosing (every 8 hours) on day 1 to day 4. Serial PK blood sample collections are planned on Day 5 after morning dosing(expected to reach steady state concentration on day 5).

❝ Kindly clarify, whether 2nd and 3rd dose on day 5 need to be administered or not? and sampling should be continued for 24 hours?

If you have evidence from peer-reviewed literature that the PK of the drug is not subjected to a circadian rhythm, the profile after the first dose in steady state is sufficient. Otherwise, you have to dose also tid on day 5 and the primary PK metric for the extent of absorption will be AUCss,0–24h. A ‘classical’ example is theophylline.

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dshah
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India/United Kingdom,
2024-01-22 11:09
(41 d 15:43 ago)

@ NK
Posting: # 23837
Views: 781
 

 Steady state BE study dosing

Hi NK!

❝ Kindly clarify, whether 2nd and 3rd dose on day 5 need to be administered or not? and sampling should be continued for 24 hours?


So you are asking for protocol preparation consideration. The study is in healthy volunteers- so I believe that AUC0-t/AUC0-inf>=0.8 also needs to be followed, so consider sampling accordingly.

Regards,
Divyen
Helmut
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Vienna, Austria,
2024-01-27 23:01
(36 d 03:50 ago)

@ dshah
Posting: # 23842
Views: 461
 

 AUC in steady state

Hi Divyen,

❝ So you are asking for protocol preparation consideration. The study is in healthy volunteers- so I believe that AUC0-t/AUC0-inf>=0.8 also needs to be followed, so consider sampling accordingly.

Here you err. Neither AUC0–t nor AUC0– are PK metrics of the extent of absorption in steady state.

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dshah
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India/United Kingdom,
2024-01-27 23:06
(36 d 03:45 ago)

@ Helmut
Posting: # 23843
Views: 456
 

 AUC in steady state

Hi Helmut!
Thank you for correcting me.
Seems an EMA Study because of steady state requirement.
Regards,
Divyen
Helmut
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2024-01-27 23:16
(36 d 03:35 ago)

@ dshah
Posting: # 23844
Views: 466
 

 AUC in steady state

Hi Divyen,

❝ Thank you for correcting me.

No worries, I err all the time… :-D
Background and some ideas.

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