Table 6. Bioequivalence Assessment for AK1BIOVAIL 2548
|
|
Geometric
Mean |
Ratio of |
90% CI for the Ratio |
|
|
|
Reference |
Test |
Geometric |
Geometric Means |
|
|
|
|
Means |
|
|
Bupropion Cmax
(ng/ml) AUC0-t (ng*h/ml) AUC0-∞
(ng*h/ml) |
143.2 1540.5 1589.8 |
132.2 1696.2 1751.4 |
0.92 1.10 1.10 |
(0.84, 1.01) (1.04, 1.17) (1.04, 1.16) |
|
Bupropion Erythroamino Alcohol Cmax
(ng/ml) AUC0-t (ng*h/ml) AUC0-∞ (ng*h/ml) |
29.3 1476.7 1648.1 |
34.6 1674.5 1902.6 |
1.18 1.13 1.15 |
(1.10, 1.26) 1.04, 1.24) 1.05, 1.27) |
|
Bupropion Threoamino Alcohol Cmax
(ng/ml) AUC0-t (ng*h/ml) AUC0-∞ (ng*h/ml) |
159.0 7511.6 9568.3 |
186.9 8444.8 10969.0 |
1.18 1.15 1.12 |
(1.11, 1.25) 1.04, 1.26) 1.04, 1.21) |
|
Hydroxybupropion Cmax (ng/ml) AUC0-t (ng*h/ml) AUC0-∞ (ng*h/ml) |
378.5 17054.3 17786.1 |
416.3 17695.7 18601.3 |
1.10 1.05 1.04 |
(1.03, 1.17) 0.96, 1.12) 0.97, 1.13) |
|
PAWC Cmax (µM) AUC0-t
(µM*h) AUC0-∞ (µM*h) |
1.49 55.3 58.3 |
1.5 58.2 61.9 |
1.02 1.06 1.05 |
(0.97, 1.08) 0.98, 1.13) 0.99, 1.14) |
Reanalysis of the data
by the reviewer was in agreement with that provided by the sponsor regarding
the bioequivalence during the test and reference periods.
No evidence of dose dumping
after administration with food was observed, with Cmax for bupropion
in both periods occurring at approximately 5 hours, in agreement with tmax
observed in the previous single dose and multiple dose studies of WELLBUTRIN
XL (AK1BIOVCAIL2751 and AK1BIOVAIL2543).
The 90% confidence
intervals on the geometric means of the Cmax and AUC ratios are
within the bioequivalence interval of 0.8 to 1.25 for bupropion and for the
predominant metabolite hydroxybupropion.
They are outside of the bioequivalence interval for the Cmax and AUC0-∞
for bupropion erythroamino [blacked out] and (1.05, 1.27), respectively, and the AUC0-t
for bupropion threoamino alcohol (1.04, 1.26).
This was due to an approximate [blacked out] and 13% increase in bupropion erythroamino Cmax and
AUC0-∞, respectively and an approximate 8% increase in
bupropion threoamino AUC0-t.
The Sponsor has noted a
significant sequence effect for Cmax for bupropion. The source of this effect is unknown. The sequences were balanced with respect to age, race, weight and
body mass index. There were fewer women
in Sequence AB than in Sequence BA. All
concentrations of bupropion at the beginning of the second period were BQL. Thus the sequence effect is not due to
carryover of bupropion.
72
Back a Page
Next Page
Back to Wellbutrin XL NDA Index Page
Back to Main Index Page