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
Epinastine
Epinastine
CLINICAL PHARMACOLOGY
Epinastine is a topically active, direct H1-receptor
antagonist and an inhibitor of the release of histamine from the mast
cell. Epinastine is selective for the histamine H1-receptor and has affinity
for the histamine H2 receptor. Epinastine also possesses affinity for
the a1-, a2-, and 5-HT2 –receptors. Epinastine does not penetrate
the blood/brain barrier and, therefore, is not expected to induce side
effects of the central nervous system.
Fourteen subjects, with allergic conjunctivitis, received one drop
of ELESTAT™ in each eye twice daily for seven days. On day seven
average maximum epinastine plasma concentrations of 0.04 ± 0.014
ng/ml were reached after about two hours indicating low systemic exposure.
While these concentrations represented an increase over those seen following
a single dose, the day 1 and day 7 Area Under the Curve (AUC)
values were unchanged indicating that there is no increase in systemic
absorption with multiple dosing. Epinastine is 64% bound to plasma
proteins. The total systemic clearance is approximately 56 L/hr and the
terminal plasma elimination half-life is about 12 hours. Epinastine is
mainly excreted unchanged. About 55% of an intravenous dose is recovered
unchanged in the urine with about 30% in feces. Less than 10%
is metabolized. The renal elimination is mainly via active tubular secretion.
Clinical studies: Epinastine HCl 0.05% has been shown
to be significantly superior to vehicle for improving ocular itching in
patients with allergic conjunctivitis in clinical studies using two different
models: (1) conjunctival antigen challenge (CAC) where patients were dosed
and then received antigen instilled into the inferior conjunctival fornix;
and (2) environmental field studies where patients were dosed and evaluated
during allergy season in their natural habitat. Results demonstrated a
rapid onset of action for epinastine HCl 0.05% within 3 to 5 minutes
after conjunctival antigen challenge. Duration of effect
was shown to be 8 hours, making a twice daily regimen suitable. This dosing
regimen was shown to be safe and effective for up to 8 weeks, without
evidence of tachyphylaxis.
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