Bioequivalence and Bioavailability Forum • Steady state BE study dosing

NK
☆

India,
2024-01-19 05:24
(100 d 03:00 ago)

Posting: # 23832
Views: 1,401

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
★★★

Vienna, Austria,
2024-01-20 13:50
(98 d 18:34 ago)

@ NK
Posting: # 23834
Views: 1,211

Circadian rhythm?

Post reply

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 AUC_ss,0–24h. A ‘classical’ example is theophylline.

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

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

dshah ★★ India/United Kingdom, 2024-01-22 11:09 (96 d 21:15 ago) @ NK Posting: # 23837 Views: 1,197	Steady state BE study dosing Post reply
	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
★★★

Vienna, Austria,
2024-01-27 23:01
(91 d 09:23 ago)

@ dshah
Posting: # 23842
Views: 869

AUC in steady state

Post reply

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 AUC_0–t nor AUC_0–∞ are PK metrics of the extent of absorption in steady state.

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

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

dshah ★★ India/United Kingdom, 2024-01-27 23:06 (91 d 09:18 ago) @ Helmut Posting: # 23843 Views: 862	AUC in steady state Post reply
	Hi Helmut! Thank you for correcting me. Seems an EMA Study because of steady state requirement. Regards, Divyen

Helmut ★★★ Vienna, Austria, 2024-01-27 23:16 (91 d 09:08 ago) @ dshah Posting: # 23844 Views: 865	AUC in steady state Post reply
	Hi Divyen, ❝ Thank you for correcting me. No worries, I err all the time… Background and some ideas. — Dif-tor heh smusma 🖖🏼 Довге життя Україна! Helmut Schütz The quality of responses received is directly proportional to the quality of the question asked. 🚮 Science Quotes