A comparative study of a preservative-free latanoprost cationic emulsion (Catioprost) and a BAK-preserved latanoprost solution in animal models.
OBJECTIVE
Benzalkonium chloride (BAK), a common preservative in eye drops, can induce ocular surface toxicity that may decrease glaucoma therapy compliance. The ocular hypotensive effect, pharmacokinetic (PK) profiles, and local tolerance of a preservative-free latanoprost 0.005% cationic emulsion (Catioprost(®)), and a BAK-preserved latanoprost 0.005% solution (Xalatan(®)), were compared.


METHODS
The ocular hypotensive effect was evaluated in monkeys with elevated intraocular pressure (IOP) induced by laser photocoagulation of the trabecular meshwork. Each monkey (n=8) received both latanoprost formulations once daily for 5 consecutive treatment days in a crossover design with at least a 2-week washout period between treatments. IOP was measured at baseline (on day 1, no instillation), on vehicle treatment day (day 0), and on treatment days 1, 3, and 5 before drug instillation and then hourly for 6 h. In rabbits, the ocular and systemic concentrations of latanoprost free acid were determined following a single instillation and the local tolerance of twice daily instillations over 28 days was assessed.


RESULTS
Both the preservative-free and BAK-preserved latanoprost formulations shared the same efficacy profile with the maximum IOP reduction occurring 2 h after each morning dose (-15%, -20%, and -26%; -15%, -23%, and -23% on days 1, 3, and 5, respectively) and lasting through 24 h. The equivalence in efficacy was confirmed by the PK data demonstrating similar area under the curves (AUCs). While both formulations were well tolerated, the incidence of conjunctival hyperemia was reduced by 42% with the BAK-free latanoprost cationic emulsion.


CONCLUSIONS
In animal models, a preservative-free latanoprost cationic emulsion was as effective as Xalatan(®) for lowering IOP with an improved ocular tolerance profile.
Novagali Pharma, Evry, France.
Philippe
P
Daull
Ronald
R
Buggage
Grégory
G
Lambert
Marie-Odile
MO
Faure
Janet
J
Serle
Rong-Fang
RF
Wang
Jean-Sébastien
JS
Garrigue
D000818:Animals; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001548:Benzalkonium Compounds / Q000737:chemistry*; D002412:Cations; D002626:Chemistry, Pharmaceutical; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004655:Emulsions; D005123:Eye / Q000187:drug effects / Q000378:metabolism; D005260:Female; D007429:Intraocular Pressure / Q000187:drug effects*; D000077338:Latanoprost; D008252:Macaca fascicularis; D008297:Male; D009798:Ocular Hypertension / Q000188:drug therapy*; D009883:Ophthalmic Solutions; D011310:Preservatives, Pharmaceutical / Q000737:chemistry*; D011461:Prostaglandins F, Synthetic / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011817:Rabbits; D014018:Tissue Distribution; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D001548:Benzalkonium Compounds; D002412:Cations; D004655:Emulsions; D009883:Ophthalmic Solutions; D011310:Preservatives, Pharmaceutical; D011461:Prostaglandins F, Synthetic; D000077338:Latanoprost