Bioequivalence and Bioavailability Forum

Dear KR!

❝ Can anyone throw some focus on dose normalization for two way crossover

❝ study? i.e if reference product is of 30 mg given once daily and test

❝ product is of 10 mg given thrice daily then how to do pharmacokinetic and

❝ statistical analysis?

Your design sounds a little bit strange. The reference obviously is an MR formulation and you want to develop an IR? Is there no IR reference available? What's the rationale to come up with an IR formulation (compliance issues)? But if you want to do that:

• the study is not a BE study (rate of BA will be different by design) but a comparative BA study
  
• compare only AUCs (no dose normalization, because the total dose in 24 hours is 30 mg for both formulations)

❝ What is the effect of this dose on concentration values?

OK, you will have three C_max values for the IR formulation. Whether they will be different or not depends on the dosage interval (thrice daily for some antibiotics means strictly 8/8/8 hours; for many drugs morning/after lunch/after dinner would mean 6/6/12 hours) and the half life of the drug (accumulation?). With some knowledge of the PK it is possible to get an idea about the expected levels for test/reference. This is useful in designing the sampling scheme. But again: it does not make sense to compare the rate of BA.