Aqueous humor pharmacokinetics of Benzalkonium chloride free bimatoprost formulated in tight junction modulation technology compared to Benzalkonium chloride preserved bimatoprost 0.01% ophthalmic solution in rabbit eyes

This study was undertaken with an objective to compare the aqueous humor pharmacokinetics (PKs) of bimatoprost and bimatoprost free acid of innovator bimatoprost 0.01% (BAK-Bimatoprost) and the novel formulation, Tight Junction Modulation technology based bimatoprost 0.01% (TJM-bimatoprost) containing polyhexamethylene Biguanide hydrochloride (PHMB) as a preservative. All animals in the study were assigned to one of two treatment arms: either a single dose of BAK-Bimatoprost (n=28) or a TJM-bimatoprost ophthalmic solution (n=28). Time points for aqueous humor collection were 0.5, 1, 2, 4, 8, 12 and 24 Hrs after drug administration. The mean Cmax of 11.93± 2.70 vs 10.92± 3.84 ng/ml was comparable (P>0.05, one-way ANOVA) across TJM bimatoprost and BAK-bimatoprost treatment arms. Results of other PK parameters pertaining to bimatoprost+ bimatoprost free acid concentration were as follows: time to maximum concentration (T_max) was 1.75± 2.0 vs 1.50 ± 1.16 hr and half-live (T_half) was 2.13 ± 0.58 vs 2.47 ± 0.79 hr in the TJM- bimatoprost and BAK-bimatoprost treatment arms respectively. Overall, there was no difference between TJM-bimatoprost and BAK-bimatoprost treatment arms in the PK end points. The results taken in totality support the hypothesis that pharmacokinetics TJM-bimatoprost 0.01%, containing PHMB preservative, is comparable to BAK-bimatoprost 0.01%. A new formulation of bimatoprost 0.01% using Tight Junction Modulation technology is pharmacokinetically comparable to marketed formulation of bimatoprost containing benzalkonium chloride preservative.