Bioequivalence and Bioavailability Forum

Baseline profile prior to each period? [Regulatives / Guidelines]

posted by Helmut  – Vienna, Austria, 2015-09-16 20:15 (3138 d 09:48 ago) – Posting: # 15410
Views: 19,319

Dear Ohlbe,

❝ ❝ … I don’t get the idea of basing BE on uncorrected data.

❝

❝ I can see one theoretical situation which could be tricky. I don't know whether you have come across anything like this.

Not only theoretically.

❝ Many endogeneous compounds follow a circadian rythm. What if the concentrations at 8 AM are higher than in the evening ? Negative concentrations after baseline correction will be replaced with 0. Couldn't this artificially decrease the difference between formulations, compared with a non-baseline-corrected analysis ? […]

Good point! In such a case one has to sample an entire blank profile (as the GL suggests) – not only one (or a few pre-dose) blanks in the morning. If I understand the GL correctly, subtraction of the pre-dose AUC from the post-dose AUC is suggested. I don’t get it. What about C_max? I always prefer to subtract concentrations.

Another point: The GL suggest a blank profile preceding each period (“to account for fluctuations in the endogenous baseline due to cir­ca­dian rhythms”). This might be difficult to achieve given the limited blood volume (especially in higher order cross-overs or replicate designs). What I did in the past (and which was accepted after a scientific advice):

• Sample an entire blank profile prior to administration in period 1 only.
  
• Sample three pre-dose samples in the other periods. Keep the interval short (i.e., maximum 30 minutes pre-dose). Take the median (my preference) or the mean (GL-disciples).
  
• Correct the blank profile for the ratio of pre-dose in period 1 and the value from above.
  
• Subtract these corrected blank-profiles from other period’s concentrations.

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


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Science Quotes

Complete thread:

• Baseline correction vs non-baseline cor­rection jag009 2015-09-15 20:29 [Regulatives / Guidelines] 
  • Baseline correction vs non-baseline correction Lucas 2015-09-16 14:16
    • Baseline correction vs non-baseline correction Relaxation 2015-09-18 10:25
  • Baseline correction or supra-thera­peu­tic dose Helmut 2015-09-16 15:16
    • Baseline correction or supra-thera­peu­tic dose Ohlbe 2015-09-16 17:55
      • Baseline profile prior to each period?Helmut 2015-09-16 18:15
      • Baseline correction examples Helmut 2015-09-17 15:44
        • Baseline correction examples Lucas 2015-09-18 14:19
          • Baseline correction examples Helmut 2015-09-18 17:28
            • Baseline correction examples Mauricio Sampaio 2016-02-07 03:05
              • Baseline correction examples Lucas 2016-02-10 11:48
                • Postmenopausal women Helmut 2016-02-10 12:26
                • Baseline correction examples Mauricio Sampaio 2016-02-11 01:38
                • Baseline correction examples Dr_Dan 2016-02-11 09:22
                  • Postmenopausal women Mauricio Sampaio 2016-02-12 03:24
                    • Postmenopausal women Dr_Dan 2016-02-15 17:45
      • Baseline; another example Helmut 2015-09-18 17:16
        • Baseline; another example nobody 2016-02-12 09:10
          • Baseline; another example Helmut 2016-02-12 13:37
            • Baseline; another example nobody 2016-02-12 14:08
              • Slowly going OT: BE study simulations Helmut 2016-02-12 15:47
                • Slowly going OT: BE study simulations nobody 2016-02-12 16:15
                  • Religious debate Helmut 2016-02-12 17:04
                    • Religious debate nobody 2016-02-12 17:26
                      • Religious debate ElMaestro 2016-02-13 12:53
                        • Religious debate nobody 2016-02-14 15:23
                • Slowly going OT: BE study simulations Ohlbe 2016-02-13 13:10
                  • Slowly going OT: BE study simulations Helmut 2016-02-13 15:02
                    • Slowly going OT: BE study simulations lizhao 2016-02-25 17:31
                      • Business as usual Helmut 2016-02-25 17:44
                        • Business as usual lizhao 2016-02-25 17:59