115
X-ray), no apparent effect on the
pharmacokinetics of bupropion or its metabolites was revealed,
116
compared
to healthy volunteers.
117
Age: The effects of age on the
pharmacokinetics of bupropion and its metabolites have not
118
been
fully characterized, but an exploration of steady-state bupropion
concentrations from
119
several
depression efficacy studies involving patients dosed in a range of 300 to 750
mg/day, on
120
a
3 times daily schedule, revealed no relationship between (18 to 83 years) and
plasma
121
concentration
of bupropion. A single-dose
pharmacokinetic study demonstrated that the
122
disposition
of bupropion and its metabolites in elderly subjects was similar to that of
younger
123
subjects. These data suggest there is no prominent
effect of age on bupropion concentration;
124
however,
another pharmacokinetic study, single and multiple dose, has suggested that the
elderly
125
are at increased risk for accumulation of bupropion and its
metabolites. (See PRECAUTIONS:
126
Geriatric Use).
127
Gender: A single-dose study involving 12 healthy male and
12 healthy female volunteers
128
revealed
no sex-related differences in the pharmacokinetic parameters of bupropion.
129
Smokers: The effect
of cigarette smoking on the pharmacokinetics of bupropion were
130
Studied
in 34 healthy male and female volunteers; 17 were chronic smokers and 17
131
were
nonsmokers. Following oral
administration of a single 150-mg dose of bupropion, there
132
was
no statistically significant difference in Cmax, Tmax,
AUC, or clearance of bupropion
133
or
its active metabolites between smokers and nonsmokers.
134
CLINICAL
TRIALS
135
The efficacy of bupropion as a treatment
for major depressive disorder was established with
136
the
immediate-release formulation of bupropion in two 4-week, placebo-controlled
trials in adult
137
inpatients
and in one 6-week, placebo-controlled trial in adult outpatients. In the first study,
138
patients
were titrated in a bupropion dose range of 300 to 600 mg/day of the
immediate-release
139
formulation
on a 3 times daily schedule; 78% of patients received maximum doses of
140
450
mg/day or less. This trial demonstrated
the effectiveness of bupropion on the Hamilton
141
Depression
Rating Scale (HDRS) total score, the depressed mood item (item 1) from that
scale,
142
and
the Clinical Global Impressions (CGI) severity score. A second study included 2 fixed doses
143
of
the immediate-release formulation of bupropion (300 and 450 mg/day) and
placebo. This trial
144
demonstrated
the effectiveness of bupropion, but only at the 450-mg/day dose of the
145
immediate-release
formulation; the results were positive for the HDRS total score and the CGI
146
severity
score, but not for HDRS item 1. In the
third study, outpatients received 300 mg/day of
147
the
immediate-release formulation of bupropion.
This study demonstrated the effectiveness of
148
bupropion
on the HDRS total score, HDRS item 1, the Montgomery-Asberg Depression Rating
149
Scale,
the CGI severity score, and the CGI improvement score.
150
Although there are no independent trials
demonstrating the antidepressant effectiveness of
151
WELLBUTRIN XL, studies have demonstrated similar bioavailability of the
immediate-release
152
and
the extended-release formulation of bupropion under steady-state conditions,
i.e.,
153
WELLBUTRIN XL 300 mg once daily was shown to have bioavailability that was similar
to that
4
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