Bioequivalence and Bioavailability Forum

Dear Mr.Jag,

As per Canadian BE guidance “Conduct and Analysis of Comparative Bioavailability studies”, a pro-drug is to be treated as a 'parent drug'. That is, if the substance released from the dosage form is absorbed intact and is reliably measurable in the systemic circulation, it should be used in the assessment of Bioequivalence.

Fasting state:
Bioequivalence estimation of the active metabolite of the prodrug is allowed if

1. Concentration of the prodrug cannot be reliably measured
   
2. Pro-drug is not detectable due to rapid biotransformation

Fed state:
If the prodrug levels are measurable in the fed state, you need to analyse Prodrug for bioequivalence estimation.
However, quantification of its metabolite levels may sometimes be helpful, e.g., to explain extreme values caused by metabolic changes within a subject. In the above case, bioequivalence estimation will be based both on the Pro-drug and its metabolite.