Bioequivalence and Bioavailability Forum • Pharmacokinetics linearity

Pharmacokinetics linearity [Regulatives / Guidelines]

posted by pjs – India, 2015-05-28 14:26 (3587 d 14:57 ago) – Posting: # 14865
Views: 4,567

Dear all,

Further to this post.

As mentioned pharmacokinetics is linear after IV administration of 2-10 mg. Hence can it be assumed that metabolism and elimination are linear in this range?? Hence if absorption is linear after oral administration in this dose range can linearity be suggested? Also what can be reasons for nonlinearity at lower dose? The drug is BCS class3 but if it would be BCS class1 than can no difference in absorption be assumed and linearity be suggested (not intended drug but just hypothetical case)?
Another option is doing BE study at higher strength 25 mg and after successfully completing it, using the same subjects to dose 5 mg and extrapolating linearity in terms of Cmax and AUC.
What about regulatory acceptance?
If Cmax and AUC data are available for the dose 25 mg and 50mg and lndose vs lnAUC pass through 0 can linearity be assumed for 5 mg also?

Please suggest.

Regards,
PJS