A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Pondimin Pharmacology, Pharmacokinetics, Studies, Metabolism - Fenfluramine
Pondimin Pharmacology, Pharmacokinetics, Studies, Metabolism - Fenfluramine
CLINICAL PHARMACOLOGY
Fenfluramine is a sympathomimetic
amine, the pharmacologic activity of which differs somewhat from
that of the prototype
drugs of this class used in obesity,
the amphetamines, in appearing to produce more central nervous system
depression than stimulation.
The mechanism of
action of Fenfluramine
HCl is unclear but may be related to brain
levels (or turnover rates) of serotonin
or to increased glucose utilization. The antiappetite effects of
Fenfluramine HCl are suppressed by serotonin-blocking drugs and
by drugs that lower brain
levels of the amine. Furthermore, decreased serotonin
levels produced by selective brain lesions suppress the action
of Fenfluramine HCl.
In a study of 20 normal
males, fenfluramine increased glucose
utilization, resulting in decreased blood
glucose levels. Experimental
work in animals suggested
that increased glucose
utilization activated the satiety
center and decreased the activity
of the feeding center.
Perhaps by this mechanism Fenfluramine HCl inhibits appetite. The
relationship between glucose
utilization and serotonin
has not been clarified.
Fenfluramine is well-absorbed from the gastrointestinal
tract, and a maximal anorectic
effect is generally seen
after 2 to 4 hours. In man,
fenfluramine is de-ethylated to norfenfluramine which is subsequently
oxidized to m-trifluoromethyl benzoic acid
and excreted as the glycine
conjugate, m-trifluoromethylhippuric acid. Other compounds found
in the urine include unchanged
fenfluramine and norfenfluramine.
The rate of excretion
of fenfluramine is pH dependent,
with much smaller amounts appearing in an alkaline
than in an acid urine.
The half-life of
fenfluramine is said to be about 20 hours, compared with 5 hours
for amphetamines; however, if urinary
excretion is rapid
and the pH maintained in
the acidic range (below
pH 5), half-life
can be reduced to 11 hours. Fenfluramine and norfenfluramine reach
steady state concentrations
in plasma within 3 to
4 days following chronic
dosage.
The greatest weight
loss is seen in those patients
who maintain the highest levels of Fenfluramine HCl. A 2-to-3-kg
weight loss
over 6 weeks is associated with a plasma
level of 0.1 mcg/ml (or 10 mcg/100 ml).
Fenfluramine is widely distributed in almost all body
tissues. It is soluble in lipids and crosses the blood-brain barrier.
Fenfluramine crosses the placenta
readily in monkeys.
top
