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
Elocon Pharmacology, Pharmacokinetics, Studies, Metabolism - Mometasone Furoate
Elocon Pharmacology, Pharmacokinetics, Studies, Metabolism - Mometasone Furoate
CLINICAL PHARMACOLOGY
Cream and Ointment
Like other topical
corticosteroids, mometasone furoate has anti-inflammatory, anti-pruritic,
and vasoconstrictive
properties. The mechanism
of the anti-inflammatory activity of the topical
steroids, in general, is unclear. However, corticosteroids are thought
to act by the induction
of phospholipase
A2 inhibitory proteins, collectively called lipocortins.
It is postulated that these proteins control
the biosynthesis
of potent mediators of
inflammation such
as prostaglandins and leukotrienes by inhibiting the release
of their common precursor arachidonic acid. Arachidonic acid
is released from membrane phospholipids by phospholipase
A2.
Lotion
The corticosteroids are a class
of compounds comprising steroid
hormones secreted by the adrenal
cortex and their synthetic
analogs. In pharmacologic
doses corticosteroids are used primarily for their anti-inflammatory
and/or immunosuppressive effects.
Topical corticosteroids, such as mometasone furoate, are effective
in the treatment of
corticosteroid-responsive dermatoses primarily because of their
anti-inflammatory, anti-pruritic, and vasoconstrictive
actions. However, while the physiologic, pharmacologic, and clinical
effects of the corticosteroids are well known, the exact mechanisms
of their actions in each disease
are uncertain. Mometasone furoate has been shown to have topical
(dermatologic) and systemic
pharmacologic and metabolic effects characteristic of this class
of drugs.
Pharmacokinetics
Cream and Ointment: The extent of percutaneous
absorption of topical
corticosteroids is determined by many factors including the vehicle
and the integrity of the epidermal barrier. Occlusive dressings
with hydrocortisone
for up to 24 hours have not been demonstrated to increase penetration;
however, occlusion
of hydrocortisone
for 96 hours markedly enhances penetration.
Studies in humans indicate that approximately 0.4% of the applied
dose of mometasone furoate cream
and ointment 0.1% [0.7%
of ointment] enters the circulation
after 8 hours of contact
on normal skin
without occlusion. Inflammation and/or other disease
processes in the skin may
increase percutaneous absorption. Studies performed with mometasone
furoate cream and ointment
indicate that it is in the medium
range of potency as compared
with other topical corticosteroids.
In a study evaluating the effects of mometasone furoate ointment on the hypothalamic-
pituitary-adrenal (HPA) axis, 15 grams were applied twice daily for 7 days to
six adult patients with psoriasis or atopic dermatitis. The ointment was applied without
occlusion to at least 30% of the body surface. The results show that the drug caused a
slight lowering of adrenal corticosteroid secretion.
In a pediatric trial,
24 atopic dermatitis
patients, of which 19 patients were age
2 to 12 years, were treated with mometasone furoate cream
and 0.1% once daily. The majority of patients cleared within 3 weeks.
Lotion: The extent of percutaneous
absorption of topical
corticosteroids is determined by many factors including the vehicle,
the integrity of the epidermal barrier, and the use of occlusive
dressings. (See DOSAGE AND ADMINISTRATION).
Topical corticosteroids can be absorbed from normal
intact skin.
A study using a radio-labelled 3H mometasone furoate
ointment (0.1%) formulation was performed in man
to measure systemic
absorption and excretion. Results showed that approximately 0.7%
of the steroid was absorbed
during 8 hours of contact, without occlusion, with intact skin of
normal volunteers. A
similar minimal degree
of absorption of
the corticosteroid from the lotion
formulation would be anticipated.
Inflammation and/or disease
processes in the skin increase
percutaneous absorption. Occlusive dressings substantially increase
the percutaneous absorption of topical
corticosteroids. (See DOSAGE AND ADMINISTRATION).
Mometasone furoate lotion
was applied at 15 ml twice
daily (30 ml per day) to
diseased skin (patients
with scalp and body psoriasis)
of four patients for seven days, to study its effects on the hypothalamic-pituitary-adrenal
(HPA) axis. Plasma cortisol
levels for each of the four patients remained well within the normal
range and changed little
from baseline.
Once absorbed through the skin, topical
corticosteroids are handled through pharmacokinetic pathways similar
to systemically administered corticosteroids. Corticosteroids are
bound to plasma
proteins in varying degrees. Corticosteroids are metabolized primarily
in the liver and are then
excreted by the kidneys. Some of the topical
corticosteroids and their metabolites are also excreted into the
bile.
top
