Biomedical Engineering Reference
In-Depth Information
The recommended dosing regimen for infected eye is one drop twice
a day in each eye approximately 12 h apart. Single-center, masked,
prospective, randomized, longitudinal trial was conducted for 12
months with 0.05 % cyclosporine (RESTASIS
®
) and artificial tears
twice daily. Dry eye signs and symptoms have been evaluated at
baseline and months 4, 8, and 12. Baseline sign and symptoms were
proportional with the disease severity level 2 and 3 comparable in
both groups (
P
0.05). Results demonstrated an improvement in
Schirmer test scores, tear breakup time, and ocular surface disease
scores (
P
>
0.01) relative to artificial tears at 8 and 12 months,
respectively. Study results indicated that RESTASIS
®
may slow or
prevent disease progression in patients with dry eye at severity level
2or3[
23
].
Drug Composition
: Each milliliter of RESTASIS
®
emulsion con-
tains 0.5 mg of active drug (0.05 % cyclosporine), glycerin, castor
oil, polysorbate 80, carbomer copolymer type A, purified water,
and sodium hydroxide (to adjust pH between 6.5 and 8.0).
Pharmacodynamic Profile
: Cyclosporine is a cyclic undecapeptide,
an active metabolite from
Tolypocladium inflatum
. In individuals
suffering from poor tear production due to ocular inflammations
associated with keratoconjunctivitis sicca, cyclosporine acts as an
immunomodulator. The exact mechanism by which the active
induces tear production is unclear.
<
Pharmacokinetic Profile
: Following topical application of RESTA-
SIS
®
0.05 % twice daily, blood concentrations were below the quan-
titation limit of 0.1 g/mL in humans. Results demonstrated that
there was no detectable drug accumulation in blood for the entire
study period. Similarly, ocular tissue distribution of cyclosporine post
topical administration to albino rabbits and beagle dogs was studied
[
24
]. Results demonstrated rapid absorption of cyclosporine into
conjunctiva (Cmax: dogs, 1,490 ng/g; rabbits, 1,340 ng/g)
and cornea (Cmax: dogs, 311 ng/g; rabbits, 955 ng/g). Lower
drug concentrations were detected in the deeper ocular tissues.
Topical ophthalmic cyclosporine penetrated deeper into extraocular
tissues to generate therapeutic immunomodulatory effect with very
low or minimal absorption into the blood circulation [
24
].
Adverse Reactions
: Although the drug product is effective in treat-
ing dry eye, several adverse effects have been reported. Adverse
reactions include ocular burning (17 %), conjunctival hyperemia,
discharge, epiphora, eye pain, foreign body sensation, pruritus,
stinging, and visual disturbances in 1-5 % of subjects. Also, few
subjects reported hypersensitivity and superficial eye injury.
ZIRGAN
®
Indications and Usage
: ZIRGAN
is a topical ophthalmic gel that
is currently indicated for the treatment of acute herpetic keratitis
(dendritic ulcers). This product was approved by the FDA in
September 2009 [
25
].
3.4
®
