Table 6. Bioequivalence Assessment for Study 2543
|
|
Geometric
Mean |
Ratio
of |
90%
CI for the |
|
|
|
Reference |
Test |
Geometric Means |
Ratio
of Geometric Means |
|
Bupropion Cmax
(ng/ml) Cmin
(ng/ml) AUC0-24
(ng*h/ml) |
165.2 31.6 1714.3 |
160.1 25.4 1531.5 |
0.97 0.80 0.89 |
(0.91,
1.03) (0.76,
0.85) (0.86,
0.93) |
|
Bupropion Erythroamino Alcohol Cmax
(ng/ml) Cmin
(ng/ml) AUC0-24
(ng*h/ml) |
116.5 81.6 2263.5 |
105.0 72.4 2057.9 |
0.90 0.89 0.91 |
(0.85,
0.96) (0.84,
0.94) (0.87,
0.95) |
|
Bupropion Threoamino Alcohol Cmax
(ng/ml) Cmin
(ng/ml) AUC0-24 (ng*h/ml) |
612.5 397.3 11609.0 |
564.8 344.3 10520.7 |
0.92 0.87 0.91 |
(0.87,
0.97) 0.82,
0.92) 0.87,
0.94) |
|
Hydroxybupropion Cmax
(ng/ml) Cmin
(ng/ml) AUC0-24 (ng*h/ml) |
1111.4 758.8 21432.6 |
1030.0 669.0 19528.1 |
0.93 0.88 0.91 |
(0.86,
1.00) (0.84,
0.93) (0.87,
0.95) |
|
PAWC Cmax (µM) Cmin
(µM*h) AUC0-24
(µM*h) |
3.8 2.4 70.1 |
3.6 2.1 63.8 |
0.95 0.88 0.91 |
(0.90,
0.99) (0.83,
0.92) (0.88,
0.95) |
No
evidence of dose dumping was observed after administration of WELLBUTRIN XL.
Reanalysis
of the data by the reviewer was in agreement with that provided by the sponsor
regarding the pharmacokinetic parameters was well as the bioequivalence of the
test and reference compounds.
The
90% confidence intervals on the geometric means of the Cmax, Cmin,
and AUC0-24 ratios are within the bioequivalence interval of 0.8 to
1.25 for bupropion and its metabolites as well as the PAWC, with the exception
of bupropion Cmin that was approximately 19% lower than that of the
Reference formulation.
Safety
The
adverse effect profiles for the test and reference products were similar. Adverse events in the run-in period included
headache, constipation, nausea, dizziness, tremor, lightheadedness, gastric
upset, chest pain, epistaxis, back pain, rash on chest, palpitations, increased
creatinine levels, and increased alanine aminotransferase levels. After the run-in period, the most common
drug-related adverse events were headache, constipation, nausea, and
dizziness. More than half
86
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