Bioequivalence and Bioavailability Forum

Dear Ioana!

❝ Can you tell me which formulation of cyclosporine can I use as reference

❝ in a bioequivalence study in an EU country: Sandimmune or Neoral?

Depending on your generic formulation.

❝ Which are the differences in bioavailability between these two

❝ formulations?

The original product was Sandimmune (soft gelatine capsules, MA 1983) developed by Sandoz (which after the merger with Ciba-Geigy in 1996 became Novartis). Later Neoral was developed (first MA in Germany 1994; patent protection started in 09/2001). The Neoral microemulsion dosage formulation is more readily absorbed than the original Sandimmune. Neoral shows a lower food effect than Sandimmune and provides greater consistency of absorption and less variation of drug exposure. Sandimmune and Neoral are not bioequivalent, therefore you must use the type of reference which matches your test product (ask your legal department whether you already can start studies with Neoral as a reference. Fascinating legal stuff of the European Court here. Note: in some European countries Neoral is marketed as Sandimmune Neoral.

See this publication:
MG Choc
Bioavailability and pharmacokinetics of cyclosporine formulations: Neoral® vs Sandimmune®
International Journal of Dermatology 36/s1: 1-6 (2008) online