Aqueous Humor Concentrations of Bimatoprost Free Acid, Bimatoprost and Travoprost Free Acid in Cataract Surgical Patients Administered Multiple Topical Ocular Doses of LUMIGAN^®or TRAVATAN^®

Abstract

Once daily topical ocular administration of LUMIGAN or TRAVATAN for 3 weeks resulted in significant concentrations of BFA and TFA in the AH. Quantifiable levels of bimatoprost amide were also measured. Maximum concentrations of BFA (30.9 nM) and TFA (3.91 nM) in the anterior chamber are sufficient to fully activate the FP prostanoid receptors in the target cells of the ciliary muscle and trabecular meshwork. Both bimatoprost in LUMIGAN and travoprost in TRAVATAN are essentially prodrugs that are rapidly hydrolyzed to their respective free acids that induce the IOP-lowering effect observed with both drugs in vivo.

Ocular pharmacokinetics of bimatoprost formulated in DuraSite compared to bimatoprost 0.03% ophthalmic solution in pigmented rabbit eyes

“…In our study, bimatoprost rapidly hydrolyzed to bimatoprost acid in the AH and ICB of rabbit eyes, reaching concentrations well above the EC 50 values (103.4 ng/mL or 248.8 nM 2 hours postdose, and 68.21 ng/g or 164.4 nM 0.5 hour postdose, respectively), which is consistent with other published preclinical and clinical data supporting the role of bimatoprost acid for lowering IOP 11,35,36. ISV-215 formulation also increased bimatoprost levels in the AH and ICB (26.57 ng/mL or 64.02 nM and 65.05 ng/mL or 156.8 nM 0.5 hour postdose, respectively), reaching reported EC 50 values for human ciliary smooth-muscle cells, compared to results with just bimatoprost 0.03% alone.…”

Phospholipid profiles of control and glaucomatous human aqueous humor

“…A possibility of an applied outcome from this research also looms in the horizon. Continued research in PG analogs beyond their original discovery in the iris [13] led to their development as effective IOP reducing topical medications like latanoprost and travoprost [53]. Lowering IOP by increasing the outflow via the conventional pathway will be close to normal physiology [54, 55].…”

Comparative Phospholipid Profiles of Control and Glaucomatous Human Trabecular Meshwork

“…4 A long period of continued research in PG analogs resulted in the development of topical glaucoma medications (such as latanoprost and travoprost) that are among the most effective IOP reducing medications used in the treatment of glaucoma. 21 The effect of other classes of lipids on IOP or outflow facility has not been well studied. Using controlled rodent experiments, it has been shown that increasing dietary omega-3 can reduce IOP due to increased outflow facility.…”