Bioequivalence and Bioavailability Forum

Dear DR_DAN,
Yes your right as per EMEA guidlines,

❝ For drugs with non-linear pharmacokinetics characterised by a more than proportional increase in AUC with increasing dose over the therapeutic dose range, the bioequivalence study should in general be conducted at the highest strength. As for drugs with linear pharmacokinetics a lower strength may be justified if the highest strength cannot be administered to healthy volunteers for safety/tolerability reasons. Likewise a higher dose may be used in case of sensitivity problems of the analytical method in line with the recommendations given for products with linear pharmacokinetics.

phenytoin having nonlinear pK by a more than proportional increase in AUC with increasing dose over the therapeutic dose range.
one more strategy in our formulation development is, it mat not possible to prepare dose proportional in all ranges of phenytoin (25 - 300mg). We are planning to formualate 25 - 100mg dose proportional and 150 - 300mg dose proportional. in this case as per above guidlines can we conduct Bioequvalence study for two highest strenghts (100mg & 300mg) of phenytoin and apply biowaiver for remaining strenghts? please advice.

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Edit: Standard quotes restored. [Helmut]