Model development and validation
The study focused on developing an optimally parameterized PK model
which can clearly capture the product characteristic as well as describe
the observed clinical PK profiles accurately. Various compartmental
models and the incorporation of product-specific characteristics such as
in-vitro dissolution profiles (Supplementary Fig 1) of the test and
reference products were tried iteratively to establish the best fit to
the observed pharmacokinetic data.
The developed model was used to simulate the original clinical study of
test and reference products in 51 virtual subjects and was assessed for
comparability based on average bioequivalence. The confidence intervals
of the Geometric mean ratio of Cmax and AUC were derived and these
results were compared with the corresponding BE results from observed
clinical data for the reference and test product.