75
ELIMINATION: Following oral administration of 200 mg of 14C-bupropion
in humans, 87% and
76
10%
of the radioactive dose were recovered in the urine and feces,
respectively. However, the
77
fraction
of the oral dose of bupropion excreted unchanged was only 0.5%, a finding
consistent
78
with
the extensive metabolism of bupropion.
79
Population Subgroups: Factors or conditions
altering metabolic capacity (e.g., liver disease,
80
congestive
heart failure (CHF), age, concomitant medications, etc.) or elimination may be
81
expected
to influence the degree and extent of accumulation of the active metabolites of
82
bupropion. The elimination of the major metabolites of
bupropion may be affected by reduced
83
renal
or hepatic function because they are moderately polar compounds and are likely
to undergo
84
further
metabolism or conjugation in the liver prior to urinary excretion.
85
Hepatic: The effect of hepatic impairment on the
pharmacokinetics of bupropion was
86
characterized
in 2 single-dose studies, one in patients with alcoholic liver disease and one
in
87
patients
with mild to severe cirrhosis. The
first study showed that the half-life of
88
hydroxybupropion
was significantly longer in 8 patients with alcoholic liver disease than in
89
8
healthy volunteers (32±14 hours versus 21±5 hours, respectively). Although not statistically
90
significant,
the AUCs for bupropion and hydroxybupropion were more variable and tended to be
91
greater
(by 53% to 57%) in patients with alcoholic liver disease. The differences in half-life for
92
bupropion
and the other metabolites in the 2 patient groups were minimal.
93
The second study showed no statistically
significant differences in the pharmacokinetics of
94
bupropion
and its active metabolites in 9 patients with mild to moderate hepatic
cirrhosis
95
compared
to 8 healthy volunteers. However, more
variability was observed in some of the
96
pharmacokinetic
parameters for bupropion (AUC, Cmax, and Tmax) and its
active metabolites (t1/2)
97
in
patients with mild to moderate hepatic cirrhosis. In addition, in patients with severe hepatic
98
cirrhosis,
the bupropion Cmax and AUC were substantially increased (mean
difference: by
99
approximately
70% and 3-fold, respectively) and more variable when compared to values in
100
healthy
volunteers; the mean bupropion half-life was also longer (29 hours in patients
with
101
severe
hepatic cirrhosis vs 19 hours in healthy subjects). For the metabolite hydroxybupropion
102
the
mean Cmax was approximately 69% lower. For the combined amino-alcohol isomers
103
threohydrobupropion
and erythrohydrobupropion, the mean Cmax was approximately 31%
lower.
104
The
mean AUC increased by about 1 1/2-fold for hydroxybupropion and about 2
1/2-fold for
105
threo/erythrohydrobupropion. The median Tmax was observed 19
hours later for
106
hydroxybupropion
and 31 hours later for threo/erythrohydrobupropion. The mean half-lives for
107
hydroxybupropion
and threo/erythrohydrobupropion were increased 5- and 2-fold, respectively,
108
in
patients were server hepatic cirrhosis compared to healthy volunteers (See WARNINGS,
109
PRECAUTIONS, and DOSAGE AND ADMINISTRATION).
110
Renal: The effect of renal disease on the pharmacokinetics
of bupropion has not been
111
studied. The elimination of the major metabolites of
bupropion may be affected by reduced rental
112
function.
113
Left Ventricular Dysfunction: During a chronic dosing study with bupropion in
114
14
depressed patients with left ventricular dysfunction (history of CHF or an
enlarged heart on
3
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