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
Feldene Pharmacology, Pharmacokinetics, Studies, Metabolism - Piroxicam
Feldene Pharmacology, Pharmacokinetics, Studies, Metabolism - Piroxicam
CLINICAL PHARMACOLOGY
FELDENE has shown anti-inflammatory, analgesic,
and antipyretic
properties in animals. Edema, erythema,
tissue proliferation,
fever, and pain
can all be inhibited in laboratory
animals by the administration
of FELDENE. It is effective regardless of the etiology
of the inflammation. The mode of action
of FELDENE is not fully established at this time. However, a common
mechanism for the
above effects may exist in the ability
of FELDENE to inhibit the biosynthesis
of prostaglandins, known mediators of inflammation.
It is established that FELDENE does not act
by stimulating the pituitary-adrenal axis.
FELDENE is well absorbed following oral
administration. Drug plasma concentrations are proportional for
10 and 20 mg doses, generally peak within three to five hours
after medication,
and subsequently decline with a mean
half-life of 50 hours
(range of 30 to 86 hours, although values outside of this range
have been encountered).
This prolonged half-life
results in the maintenance of relatively stable plasma concentrations
throughout the day on once daily doses and to significant drug accumulation
upon multiple dosing.
A single 20 mg dose
generally produces peak piroxicamplasma levels of 1.5 to 2 mcg/mL,
while maximum drug plasma
concentrations, after repeated daily ingestion
of 20 mg FELDENE, usually stabilize at 3-8 mcg/mL. Most
patients approximate steady state
plasma levels within
7 to 12 days. Higher levels, which approximate steady state
at two to three weeks, have been observed in patients in whom longer
plasma half-lives of
piroxicam occurred.
FELDENE and its biotransformation
products are excreted in urine
and feces, with about twice as much appearing in the urine
as the feces. Metabolism occurs by hydroxylation at the 5 position
of the pyridyl side chain
and conjugation
of this product; by cyclodehydration; and by a sequence of reactions
involving hydrolysis
of the amide linkage,
decarboxylation, ring contraction, and N-demethylation. Less than
5% of the daily dose is
excreted unchanged.
Concurrent administration
of aspirin (3900 mg/day)
and FELDENE (20 mg/day), resulted in a reduction
of plasma levels of piroxicam
to about 80% of their normal
values. The use of FELDENE in conjunction with aspirin
is not recommended because data are inadequate to demonstrate that
the combination produces greater improvement than that achieved
with aspirin alone and the potential
for adverse reactions is increased. Concomitant administration of
antacids had no effect
on FELDENE plasma levels.
The effects of impaired renal
function or hepatic
disease on plasma
levels have not been established.
FELDENE, like salicylates and other nonsteroidal anti-inflammatory
agents, is associated with symptoms of gastrointestinal
tract irritation
(see ADVERSE REACTIONS).
However, in a study utilizing 51Cr-tagged red blood
cells, 20 mg of FELDENE administered as a single dose
for four days did not result in a significant
increase in fecal blood
loss and did not detectably affect
the gastric mucosa.
In the same study a total
daily dose of 3900 mg
of aspirin, i.e., 972 mg q.i.d., caused a significant
increase in fecal blood
loss and mucosal lesions
as demonstrated by gastroscopy.
In controlled clinical
trials, the effectiveness
of FELDENE (piroxicam) has been established for both acute
exacerbations and long-term management of rheumatoid
arthritis and osteoarthritis.
The therapeutic
effects of FELDENE are evident early in the treatment of both diseases
with a progressive
increase in response
over several (8-12) weeks. Efficacy is seen in terms of pain
relief and
when present, subsidence of inflammation.
Doses of 20 mg/day FELDENE display a therapeutic
effect comparable to
therapeutic doses
of aspirin, with a lower incidence
of minor gastrointestinal
effects and tinnitus.
FELDENE has been administered concomitantly with fixed doses of
gold and corticosteroids. The existence of a "steroid-sparing"
effect has not been adequately studied to date.
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