Bioequivalence and Bioavailability Forum

Dear All

Regards

I have one doubt regarding the BE RLD strengths for conjugated estrogen (Premarin) and conjugated estrogen/ medroxyprogesterone (Prempro).
Premarin has following bio strengths : 1.25 mg (fast and Fed), 0.9 (fast), 0.625 and 0.45 (waiver)
For Prempro: 4 strengths are RLDs i.e. ( 0.3 mg/1.5 mg and 0.45 mg/1.5 mg, 0.625 mg/2.5 mg and 0.625 mg/5 mg)

On Prempro label it clearly says that,
Dose Proportionality: The Cmax and AUC values for MPA observed in two separate pharmacokinetic studies conducted with 2 PREMPRO 0.625 mg/2.5 mg or 2 PREMPRO or PREMPHASE 0.625 mg/5 mg tablets exhibited nonlinear dose proportionality; doubling the MPA dose from 2 x 2.5 to 2 x 5 mg increased the mean Cmax and AUC by 3.2- and 2.8-fold, respectively.

The dose proportionality of estrogens and medroxyprogesterone acetate was assessed by combining pharmacokinetic data across another two studies totaling 61 healthy, postmenopausal women. Single conjugated estrogens doses of 2 x 0.3 mg, 2 x 0.45 mg, or 2 x 0.625 mg were administered either alone or in combination with medroxyprogesterone acetate doses of 2 x 1.5 mg or 2 x 2.5 mg. Most of the estrogen components demonstrated dose proportionality; however, several estrogen components did not. Medroxyprogesterone acetate pharmacokinetic parameters increased in a dose-proportional manner.

What could be the reason behind asking for BE study for all strengths??
Can anyone guide me??

I am totally confused!!!
Help me out!!!


Thanks in advance!!!