Bioequivalence and Bioavailability Forum • OROS residence time

OROS residence time [Design Issues]

posted by Helmut – Vienna, Austria, 2012-09-13 16:28 (5033 d 16:31 ago) – Posting: # 9200
Views: 7,239

Hi ABE1580!

❝ Dear Sir,

▲ Not interested in madams’ opinions?

❝ Will it be acceptable to the FDA; if we keep option of excluding the volunteer based on the residence time of dosage form in GIT in case of Osmotic drug delivery system (ODDS)?

No way.

❝ […] In case of ODDS the tablets stay for more time in GIT and that leads to variability. Say in case of Test product tablets, it was there in GIT till 33 hrs and after that it was expelled in feces. But in same volunteer; the reference product expelled after 46 hrs.

BE is a surrogate of clinical efficacy. You can’t ignore variability caused by the formulation itself or the motility of the GIT. Does the label of OROS state “check your feces daily – if you don’t find a tablet there, see your physician”?

❝ So, will it be acceptable to FDA, if we predefine the exclusion criteria "The subjects will be excluded from the bioequivalence evaluation; who do not expel the tablets within 42 hrs"

No.

❝ Any such type of observation any one came accross?

I stopped peeking into my feces a long time ago. GIT in non-vegetarians is ≤72 hours (BTW, this is the rationale behind AUC₇₂ for IR formulations). Gastric motility in vegetarians might be decreased;^* I would suggest to include non-vegetarians in the study.

Prescott LF, Yoovathaworn K, Makarananda K, Saivises R, Sriwatanakul K. Impaired absorption of paracetamol in vegetarians. Br J Clin Pharmacol. 1993;36(3):237–40. free resource

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Complete thread:

OROS residence time ABE1580 2012-09-13 09:55
- OROS residence timeHelmut 2012-09-13 14:28
- OROS residence time jag009 2012-09-13 17:34
  - OROS residence time Helmut 2012-09-13 17:45
    - OROS residence time jag009 2012-09-13 19:45
      - OROS residence time ABE1580 2012-09-14 07:56
        
        OROS residence time ABE1580 2012-09-14 11:14
        
        OROS residence time Helmut 2012-09-14 13:58
        
        OROS residence time jag009 2012-09-17 16:47
        
        OROS residence time Helmut 2012-09-17 16:56
    - OROS residence time jag009 2012-09-18 17:11
    - OROS residence time drsinghs 2012-10-05 06:04
      - OROS residence time Ohlbe 2012-10-05 10:40
        
        OROS residence time drsinghs 2012-10-05 12:14
        
        And where? Helmut 2012-10-05 13:34
        
        And where? drsinghs 2012-10-05 14:16
        
        And where? Ohlbe 2012-10-05 16:00
        
        And where? jag009 2012-10-12 23:05