·
AK1BIOVAIL2543
- <Steady state study of the bioequivalence
of WELLBUTRIN XL 300 mg once daily and
WELLBUTRIN 100 mg immediate release given 100 mg three times daily
·
AK1BIOVAIL2571
- <Dosage strength equivalence
study comparing 150 mg and 300 mg WELLBUTRIN XL
·
AK1BIOVAIL2548
- <Food effect study with highest
strength WELLBUTRIN XL (300 mg)
The bioanalytical methods were validated and
documented appropriately.
The key findings with respect to the Clinical
Pharmacology and Biopharmaceutics of WELLBUTRIN XL are as follows:
·
Bioequivalence
for bupropion metabolites was demonstrated between the highest strength WELLBUTRIN
XL tablet (300 mg) and the approved immediate release product WELLBUTRIN
given as 100 mg three times daily. It
was noted in the minutes of the pre-IND meeting of October 26, 2001 that a
single positive well controlled study would be needed if the bioequivalence
study did not meet its objectives, and that metabolite pharmacokinetics would
be crucial. Although bioequivalence
could not be demonstrated for the parent compound (for which Cmin
was outside of the bioequivalence interval of 0.8 to 1.25), consideration
should be given to the active metabolites, since they are responsible for more
than 90% of the exposure following administration of bupropion. Therefore it is reasonable to suggest that
the two products were comparable in exposure.
It should be noted that
although comparable exposure was demonstrated, there are differences in the
shapes of the curves for bupropion in the WELLBUTRIN XL formulation
compared with immediate release formulation.
The clinical relevance of these differences cannot be predicted based on
the pharmacokinetics. However, the
comparable exposure and the role of the metabolites in the exposure and
pharmacologic activity support the approval of the WELLBUTRIN XL
formulation. Of note, for WELLBUTRIN
SR, although there were also differences in the shapes of the plasma
concentration curves compared to WELLBUTRIN IR, a clinical trial
demonstrated efficacy of WELLBUTRIN SR in maintaining antidepressant
response.
6
Back a Page
Next Page
Back to Wellbutrin XL NDA Index Page
Back to Main Index Page