Aqueous humor penetration of topical bimatoprost 0.01% and bimatoprost 0.03% in rabbits

Abstract

PurposeThe purpose of this study was to compare the aqueous humor concentrations of bimatoprost acid after topical instillation in rabbits of bimatoprost ophthalmic solution 0.01% and bimatoprost ophthalmic solution 0.03%, two commercially available intraocular pressure-lowering medications.MethodsMale Dutch Belted rabbits were divided into two treatment groups (four rabbits/eight eyes per group): bimatoprost 0.01% and bimatoprost 0.03%. Thirty microliters (μL) of study medication was to pically instilled into both eyes of each animal. Thirty minutes and 90 minutes after instillation, aqueous humor samples were collected. These samples were analyzed by reverse-phase high-performance liquid chromatography for bimatoprost acid concentration.ResultsFollowing a single topical ocular instillation, the bimatoprost 0.01% formulation had a lower mean aqueous humor concentration of bimatoprost acid than the bimatoprost 0.03% formulation at both 30 minutes (11.5 ± 2.1 ng/mL versus 37.8 ± 28.8 ng/mL; P = 0.17) and 90 minutes (20.8 ± 5.7 ng/mL versus 45.8 ± 14.3 ng/mL; P = 0.03) after topical instillation.ConclusionsTopical ocular instillation of bimatoprost 0.01% produced significantly lower bimatoprost acid concentration in the aqueous humor of rabbits than bimatoprost 0.03%, despite the 4-fold increase of benzalkonium chloride contained in bimatoprost 0.01%.

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

“…In vitro studies have shown that BAC improves drug penetration through the corneal epithelial layer by making tight junctions more porous 21,41. However, in a recent preclinical pharmacokinetic study comparing bimatoprost 0.01% to bimatoprost 0.03% in rabbit eyes, no improvements in bimatoprost acid ocular penetration were observed with bimatoprost 0.01% levels 3.3- and −2.2-fold lower than bimatoprost 0.03% at 30 and 90 minutes, respectively, following topical administration (bimatoprost levels were not reported) 42. To date, no comparative clinical pharmacokinetic study has been reported with the two bimatoprost concentrations to clarify the role of increasing BAC in improving ocular distribution in healthy volunteers.…”

Aqueous humor penetration of topical bimatoprost 0.01% and bimatoprost 0.03% in rabbits: response to authors

“…Any ophthalmologist or patient concerns raised by the incomplete and potentially misleading conclusion published by Ogundele and Jasek1 can be addressed with a carefully constructed pharmacokinetic study with a complete time-concentration profile. We are currently preparing a manuscript that reports the findings of such a study design.…”

“…We read with great interest the recent article by Ogundele and Jasek, 1 in which the authors concluded that bimatoprost ophthalmic solution 0.01% (Lumigan ® ; Allergan, Inc, Irvine, CA) produced lower bimatoprost acid concentration than bimatoprost ophthalmic solution 0.03% (Lumigan; Allergan, Inc) in the aqueous humor of rabbits. This conclusion was made based on two treatment time points (30 and 90 minutes) with a small sample size (n = 4) at each time point and with large variability.…”

“…Based on two data points, Ogundele and Jasek 1 hypothesized that bimatoprost 0.01% might have compromised the intraocular pressure (IOP)-lowering effect. Not only is there no reported correlation of animal pharmacokinetic and/or metabolism results to clinical efficacy, this hypothesis directly contradicts existing evidence.…”

“…In addition, Ogundele and Jasek 1 speculated that bimatoprost 0.01% might have increased the risk of ocular toxicity, based on prior publications of in vitro and animal studies that may not be relevant to patients, case series, or open-label clinical studies. This evidence is considered lower level compared with randomized, controlled trials.…”