Duotrav (travoprost, timolol) eye drops 2.5 ml.

Description

Duotrav Composition
active ingredients: travoprost, timolol;
1 ml of travoprost 40 μg, timolol 5 mg (as timolol maleate);
auxiliary substances: polyquad, propylene glycol, beckon (E 421), boric acid, sodium chloride, polyethoxylated castor oil, hydrogenated 40 (HCO-40), sodium hydroxide and / or hydrochloric acid (for pH adjustment), purified water.

Duotrav Dosage form
Eye drops.
Basic physical and chemical properties: transparent, colorless to light yellow solution.

Duotrav Pharmacotherapeutic group
Antiglaucoma drugs and miotic drugs.
ATX code S01E D51.

Pharmacodynamics
Duotrav® contains two active ingredients: travoprost and timolol maleate. These two substances reduce intraocular pressure due to a complementary mechanism of action and a combined effect that leads to an additional decrease in intraocular pressure (IOP) compared to the effect that is achieved with the use of either of these components as monotherapy.
Travoprost, an analogue of prostaglandin F2a, is its full agonist, which has a high selectivity and a high degree of affinity with FP receptors of prostaglandin; it reduces intraocular pressure by increasing the outflow of intraocular fluid along the trabecular meshwork and uveoscleral pathway. A decrease in intraocular pressure in humans begins 2 hours after the administration of the drug, and the maximum effect is achieved after 12 hours. A significant decrease in WTO persists for 24 hours after a single application.
Timolol is a non-selective blocker of beta-adrenergic receptors, does not have significant sympathomimetic and local anesthetic (membrane stabilizing) activity, as well as a direct inhibitory effect on the myocardium. Tonographic and fluorometric studies have confirmed that its main effect in humans is associated with a decrease in the formation of intraocular fluid and a slight increase in its outflow.

Pharmacokinetics
Absorption
Travoprost and timolol are absorbed through the cornea. Travoprost is a prodrug that undergoes rapid ester hydrolysis in the cornea to an active free acid. After a single administration of Duotrav® (with polyquaternium-1 as a preservative) to healthy volunteers (N = 22) for 5 days, free acid was not quantified in blood plasma samples in most of the participants (94.4%) and was generally not observed after 1 hour after the introduction. When measured (> 0.01 ng / ml), quantification limit), the concentration ranged from 0.011 to 0.03 ng / ml. The average value of the established concentration of timolol Cmax after a single dose of Duotrav® was 1.34 ng / ml, and Tmax was about 0.69 hours.

Distribution
The free acid of travoprost can be quantified in the intraocular fluid during the first 5 hours in animals, and in human plasma – only within the first hour after the introduction of Duotrav® into the eyes. Timolol can be determined in the intraocular fluid and blood plasma of a person 12 hours after the introduction of Duotrav® into the eyes.

Metabolism
Metabolism is the main route of elimination of both travoprost and active free acid. The pathways of systemic metabolism are parallel to the pathways of metabolism of endogenous prostaglandin F2a, which are characterized by the reduction of the double bond 13-14, oxidation of the 15-hydroxyl group, and breaks of the b-oxidative upper side chain.
Timolol is metabolized in two ways. The first path is associated with the formation of an ethanolamine side chain in the thiodiazole ring, and the second is associated with the formation of an ethanol side chain in morpholinazothio and the like, a side chain with a carbonyl group adjacent to nitrogen. The half-life of timolol from blood plasma is 4 hours after instillation of Duotrav® in the eyes.

Output
Travoprost in the form of free acid and its metabolites are excreted mainly by the kidneys. Less than 2% of the ophthalmic dose of travoprost in the form of free acid is observed in urine after application to the eye. Timolol and its metabolites are mainly excreted by the kidneys. Approximately 20% of the timolol dose is excreted in the urine unchanged, and the part that remains is also excreted in the urine in the form of metabolites.

Indications
Duotrav® is indicated for lowering intraocular pressure (IOP) in adult patients with open-angle glaucoma or ocular hypertension who do not respond well to local use of beta-blockers or prostaglandin analogs.

Contraindications
Hypersensitivity to active ingredients or other components of the drug.
Hypersensitivity to other beta blockers.
Conditions accompanied by airway hyperresponsiveness, including bronchial asthma or a history of bronchial asthma, severe chronic obstructive pulmonary disease.
Sinus bradycardia, sick sinus syndrome, including sinoauricular block, block II-III degree, uncontrolled by a pacemaker.
Severe heart failure, cardiogenic shock.
Severe allergic rhinitis and corneal dystrophy.