David C. Dahlin

Absorption of Topical Moxifloxacin Ophthalmic Solution Into Human Aqueous Humor

Purpose: To investigate the absorption of moxifloxacin into human aqueous humor after administration of moxifloxacin hydrochloride ophthalmic solution, 0.5% as base. Methods: Cataract patients were randomly allocated to receive 1 drop every 15 minutes for 4 doses before surgery (group 1) or 1 drop 4 times per day on the day before surgery plus the same preoperative regimen as group 1 (group 2). The last dose was administered 0.25, 0.50, 1, 2, or 3 hours before aqueous humor sampling. Samples from 30 patients per group were analyzed by a validated HPLC/MS/MS method. Results: For group 1, the mean ± SD Cmax was 1.50 ± 0.75 μg/mL and occurred at 0.5 hour after dosing. The mean Cmax for group 2 was 1.74 ± 0.66 μg/mL and was reached at 1 to 2 hours. Mean AUC0-3h for groups 1 and 2 were 3.16 ± 0.29 and 4.41 ± 0.48 μg·h/mL, respectively. The difference in AUC0-3h was statistically significant (P = 0.04), but the difference in Cmax was not. Conclusions: Topical moxifloxacin was well absorbed. Maximum moxifloxacin concentrations were approximately 30 times higher than the median MICs for common pathogens in bacterial endophthalmitis, indicating that either regimen may provide sufficient concentrations to prevent postoperative endophthalmitis.

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®

PURPOSE To quantify the aqueous humor (AH) concentrations of bimatoprost (amide), travoprost (isopropyl ester), and their hydrolysis products, bimatoprost free acid (BFA) and travoprost free acid (TFA), after multiple topical ocular doses of LUMIGAN and TRAVATAN, respectively, in patients awaiting cataract surgery. METHODS In 2 separate open-label, sparse-sampling trials, glaucoma patients with cataracts received LUMIGAN (bimatoprost ophthalmic solution, 0.03%) or TRAVATAN (travoprost ophthalmic solution, 0.004%) bilaterally once daily for at least 21 days prior to cataract surgery. Anterior chamber paracentesis was performed at selected times up to 5 h after the last dose and an AH sample was collected. AH samples were assayed by an independent bioanalytical laboratory using a sensitive and validated tandem LC-MS/MS method. The assay lower limits of quantitation were 0.59 nM for bimatoprost, 0.29 nM for BFA, and 0.44 nM for TFA. RESULTS AH concentrations of BFA (17-phenyl-trinor PGF(2alpha)) were quantifiable in all but one sample at 0.5 h. The maximum concentration achieved (C(max)) of BFA was 30.9 + or - 16.41 nM (n =5), observed at 2 h postdose. AH concentrations of bimatoprost amide were lower than BFA at all time points, with a C(max) of 6.81 + or - 1.36 nM (n = 7) at 1 h postdose. For TFA, measurable AH concentrations were obtained at all time points with a TFA C(max) of 3.91 + or - 2.27 nM (n = 5), which was observed at 3 h after the dose (all data are mean + or - SEM). CONCLUSIONS 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.