Lacrisert Pharmacology, Pharmacokinetics, Studies, Metabolism - Cellulose

Lacrisert Pharmacology, Pharmacokinetics, Studies, Metabolism - Cellulose

CLINICAL PHARMACOLOGY

Pharmacodynamics

LACRISERT acts to stabilize and thicken the precorneal tear film and prolong the tear film breakup time which is usually accelerated in patients with dry eye states. LACRISERT also acts to lubricate and protect the eye.

LACRISERT usually reduces the signs and symptoms resulting from moderate to severe dry eye syndromes, such as conjunctival hyperemia, corneal and conjunctival staining with rose bengal, exudation, itching, burning, foreign body sensation, smarting, photophobia, dryness and blurred or cloudy vision. Progressive visual deterioration which occurs in some patients may be retarded, halted, or sometimes reversed.

In a multicenter crossover study the 5 mg LACRISERT administered once a day during the waking hours was compared to artificial tears used four or more times daily. There was a prolongation of tear film breakup time and a decrease in foreign body sensation associated with dry eye syndrome in patients during treatment with inserts as compared to artificial tears; these findings were statistically significantly different between the treatment groups. Improvement, as measured by amelioration of symptoms, by slit-lamp examination and by rose bengal staining of the cornea and conjunctiva, was greater in most patients with moderate to severe symptoms during treatment with LACRISERT. Patient comfort was usually better with LACRISERT than with artificial tears solution, and most patients preferred LACRISERT.

In most patients treated with LACRISERT for over one year, improvement was observed as evidenced by amelioration of symptoms generally associated with keratoconjunctivitis sicca such as burning, tearing, foreign body sensation, itching, photophobia and blurred or cloudy vision.

During studies in healthy volunteers, a thickened precorneal tear film was usually observed through the slit-lamp while LACRISERT was present in the conjunctival sac.

Pharmacokinetics and Metabolism

Hydroxypropyl cellulose is a physiologically inert substance. In a study of rats fed hydroxypropyl cellulose or unmodified cellulose at levels up to 5% of their diet, it was found that the two were biologically equivalent in that neither was metabolized.

Studies conducted in rats fed ¹⁴ C-labeled hydroxypropyl cellulose demonstrated that when orally administered, hydroxypropyl cellulose is not absorbed from the gastrointestinal tract and is quantitatively excreted in the feces.

Dissolution studies in rabbits showed that hydroxypropyl cellulose inserts became softer within 1 hour after they were placed in the conjunctival sac. Most of the inserts dissolved completely in 14 to 18 hours; with a single exception, all had disappeared by 24 hours after insertion. Similar dissolution of the inserts was observed during prolonged administration (up to 54 weeks).