Bioequivalence and Bioavailability Forum

Hi everyone!

Three studies compared diclofenac with the addition of B vitamins for low back pain.

1. Kuhlwein A, Meyer HJ, Koehler CO. Reduced diclofenac administration by B vitamins: results of a randomized double-blind study with reduced daily doses of diclofenac (75 mg diclofenac versus 75 mg diclofenac plus B vitamins) in acute lumbar vertebral syndromes. Klin Wochenschr 1990; 68:107–15.
   
   
2. Vetter G, Bruggemann G, Lettko M, et al. Shortening diclofenac therapy by B vitamins. Results of a randomized double-blind study, diclofenac 50 mg versus diclofenac 50 mg plus B vitamins, in painful spinal diseases with degenerative changes. Z Rheumatol 1988;47:351–62.
   
   
3. Bruggemann G, Koehler CO, Koch EM. Results of a double-blind study of diclofenac + vitamin B1, B6, B12 versus diclofenac in patients with acute pain of the lumbar vertebrae. A multicenter study. Klin Wochenschr 1990; 68:116–20.

The authors of all 3 studies reported positive results for the combination therapy, although there were no statistically significant differences reported.

The authors concluded that there is conflicting evidence that an NSAID (diclofenac) plus B vitamins are more effective than diclofenac alone for acute low back pain, and limited evidence that B vitamins do not provide additional effect to an NSAID for chronic degenerative low back pain.

In this case, if the vitamins B are part of formulation of reference product, I have the questions below:

1. I need to consider the quantification of vitamins in the bioequivalence study to prove that reference and test product are interchangeable?
   
   
2. If you answered "YES" in the question above, I would like to know why? Note with previous information: "..there is conflicting evidence that an NSAID (diclofenac) plus B vitamins are more effective than diclofenac alone for acute low back pain, and limited evidence that B vitamins do not provide additional effect to an NSAID for chronic degenerative low back pain". Therefore, I think illogical to prove the bioequivalence of compounds that don't have trusty clinical evidences.
   
   
3. On the other hand, if I made a mistake in last conclusion above (iten 2), and Vitamins can be Actives Pharmaceutical Ingredients (API), can I apply the concept of BCS? In conclusion, the vitamins may be considered candidates for biowaivers?

If all above don't make a sense, please, inform or send to me the specific guidelines.

I wait any consideration.

Regards