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Lyle Bowman, Afshin Shafiee, Eddie Hou, Kamran Hosseini; Ocular Pharmacokinetics of ISV-215 (Bimatoprost 0.03%) Formulated in a DuraSite Delivery System Compared to Lumigan in Rabbits. Invest. Ophthalmol. Vis. Sci. 2013;54(15):765.
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To compare the ocular pharmacokinetic parameters of ISV-215 (bimatoprost 0.03% formulated in DuraSite) to Lumigan 0.03% in pigmented rabbits.
The left eye of male and female rabbits (n=32/group) received either a single topical instillation of Lumigan or ISV-215. At predetermined timepoints (0.25, 0.5, 1, 2, 4, 6, 12, and 24 hours), 4 rabbits/group/timepoint were sacrificed and the bimatoprost and bimatoprost acid levels in the aqueous humor (AH) and the iris-ciliary body (ICB) were quantified using LC-MS/MS methodology. PK parameters (Cmax, Tmax, AUC0.25-24h), was determined.
Both bimatoprost and bimatoprost acid were detected in AH and ICB. ISV-215 had a 2.2-fold higher bimatoprost Cmax value than Lumigan in the AH (26.57 ± 19.16 ng/mL at 0.5 h postdose vs. 12.11 ± 21.72 ng/mL at 1 h postdose), and a 6.1-fold increase in the ICB (65.06 ± 26.20 ng/g at 0.5h postdose vs. 10.73 ± 9.01 ng/g at 0.5 h postdose). ISV-215 also achieved a 3.5-fold higher bimatoprost acid concentration (Cmax) in the AH (103.4 ± 42.36 ng/mL at 2 h postdose vs. 29.58 ± 26.37 ng/mL at 1 h postdose) and a 3.7-fold increase in the ICB (68.21 ± 33.00 ng/g at 0.5 h postdose vs. 18.38 ± 4.05 ng/g at 0.25 h postdose). Drug exposure (AUC) was similarly higher for bimatoprost and bimatoprost acid in the AH (2.0- and 3.1-fold, respectively) and in the ICB (6.6- and 3.7-fold, respectively) of ISV-215-treated animals compared to Lumigan.
DuraSite significantly improved delivery of bimatoprost and bimatoprost acid in the AH and ICB of rabbits. This improvement in pharmacokinetic parameters has the potential to enhance intraocular pressure (IOP) lowering properties of bimatoprost in patients with ocular hypertension or reducing bimatoprost levels in the ophthalmic IOP lowering medications while improving the side effect profile.
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