Biomedical Engineering Reference
In-Depth Information
Adverse Reactions
: Although effective, the most common adverse
reactions reported were blurred vision (60 %), eye irritation (20 %),
punctate keratitis (5 %), and conjunctival hyperemia (5 %).
Indications and Usage
: Lotemax
®
ointment contains a corticoste-
roid, loteprednol etabonate, indicated for the treatment of postop-
erative inflammation and pain following ocular surgery [
32
].
Dosage and Administration
: Lotemax
®
contains 0.5 % loteprednol
etabonate in the form of an ointment. Beginning 24 h after surgery,
application of this ointment is recommended in very small amounts
(approximately ½ in. ribbon) into the conjunctival sac four times
daily. Application needs to continue through the first 2 weeks of the
postoperative period.
Lotemax
®
3.5
Drug Composition
: Each gram of ointment contains 5 mg of lote-
prednol etabonate (0.5 %) and inactives such as mineral oil and
white petrolatum.
Pharmacodynamic Profile
: Loteprednol etabonate is a “soft” steroid
belonging to a unique family of glucocorticoids [
33
]. This com-
pound has good ocular and skin permeation properties similar to
“hard” steroids [
34
,
35
]. It is synthesized via structural modifica-
tions of prednisolone-related compounds to facilitate transforma-
tion to an inactive metabolite. This compound initially binds to the
type II glucocorticoid receptor. In general, corticosteroids inhibit
the inflammatory response to a variety of drugs which possibly
delay or slow healing. This class of compounds inhibits edema,
fibrin deposition, dilation of capillaries, leukocyte migration, capil-
lary and fibroblast proliferation, collagen deposition, and scar for-
mation associated with inflammation. The molecular mechanisms
involved in modulation of inflammation by corticosteroids are not
clearly delineated. However, these compounds are believed to act
by inducing phospholipase A2 inhibitory proteins, collectively
called lipocortins. It is postulated that these proteins regulate bio-
synthesis of potent mediators of inflammation such as prostaglan-
dins and leukotrienes via inhibition of release of their common
precursor arachidonic acid which is released from membrane phos-
pholipids by phospholipase A2. Also, corticosteroids are known to
inhibit prostaglandin production through several
independent
mechanisms [
36
,
37
].
Pharmacokinetic Profile
: A randomized, double-masked, placebo-
controlled, single-center trial was conducted in human volunteers
to determine the systemic exposure to loteprednol etabonate sus-
pension following its chronic, ocular instillation. Volunteers were
instructed to instill one drop in each eye eight times daily on days
0 and 1 and four times on days 2-42. However, plasma levels of
loteprednol etabonate and its major metabolite PJ-91 were below
