Olopatadine being a second-generation antihistamine, severe CNS

Olopatadine
hydrochloride is one of the recently refined second-generation, selective
histamine H1 – receptor antagonist. It is usually used to inhibit the release
of lipid mediators, such as leukotriene and thromboxane from human
polymorphonuclear leukocytes and eosinophils

It is a tricyclic compound having a chemical
structure: 11-(Z)-3-(di-methylamino) propylidene-6,11–dihydrodibenzb, e
oxepin-2-acetic acid monohydrochloride. Olopatadine
was shown to be more stable and potent compared to other commonly used
second-generation antihistamines in double-blind clinical trials. Despite being
a second-generation antihistamine,  severe CNS side effects have been reported
with olopatadine.

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Pharmacological properties

Olopatadine has shown an affinity for the
histamine H1 receptor in receptor binding in vitro studies. Studies have shown its selectivity
for histamine H1 receptor and a lack of interaction with H2 and H3 –
histaminergic, ?-adrenergic, dopaminergic, muscarinic, and numerous other
receptors have also been demonstrated Olopatadine
inhibits the histamine-enhanced expression of intercellular adhesion molecule 1
and E-selecting.

Olopatadine is more potent as an inhibitor of
histamine-enhanced tumour necrosis factor-?-stimulated adhesion molecule
expression. Olopatadine also inhibits anti-human IgE-induced
histamine release from human conjunctival tryptase/chymase-containing mast
cells. According to these data, it is
clear that olopatadine offers additional therapeutic benefits which complement
histamine H1-receptor antagonistic activities.

Tolerability and adverse events

Olopatadine has shown to have little effect on
CNS, peripheral nervous system, autonomic nervous system, cardiovascular
system, digestive and urogenital system in rats, dogs, guinea pigs, rabbits,
mice, and cats at antiallergic doses.

An extensive systemic and topical ophthalmic
toxicology profile, mutagenicity, single and multiple-dose toxicity, the effect
on reproduction, fertility, fetal development, and ocular tolerance for
olopatadine have been studied in detail, and it has been declared safe for use.

Pharmacokinetics

Olopatadine was absorbed rapidly, under fasting
conditions after a single oral administration to healthy males at doses of 5,
10, 20, 40, and 80 mg. The elimination half-lives were 7.13–9.36 h within this
dose range.

The drug-drug interaction is very unlikely to
occur, as olopatadine is excreted through renal route without extensive
metabolism.

Under both fasting and non-fasting conditions,
the renal clearance remains constant. The effect of food on the absorption of
olopatadine is unremarkable. The plasma concentrations of olopatadine at a dose
of 10 mg/body, after single oral administration in elderly subjects were higher
than those after administration to healthy subjects. However, the half-live
values were almost the same.

Metabolism

Olopatadine is also a renal clearance drug
having poor metabolism. It has no
inhibitory effect on the drug-metabolizing actions that are catalysed by the
isoforms of cytochrome P450.

Clinical studies

In one clinical study, 73 patients with chronic
urticaria were partitioned for the safety and efficacy of olopatadine at daily
doses of 2, 5, and 10 mg (b.i.d.) for 2 weeks. None of the groups showed
serious adverse effects, and thus, olopatadine was considered highly useful in
the dose range of 2–10 mg/day.

A
study for the purpose of investigating the safety and efficacy of olopatadine
on long-term administration using the 10 mg/day dose for 8 weeks in a total of
82 patients was conducted. The only adverse effects observed after 20 days of
administration were sleepiness and increase in body weight in one patient each.
Hence, it was concluded that olopatadine would also be highly useful on
long-term administration with significantly lower incidence of adverse
reactions.

Olopatadine was compared with cetirizine for its
suppressive effects on histamine-induced wheal and flare reaction in a
double-blind, cross-over, placebo-controlled study. Olopatadine was found to
have comparable effects to cetirizine.

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