Pharmacokinetics and aqueous humor penetration of levofloxacin 1.5% and moxifloxacin 0.5% in patients undergoing cataract surgery

Abstract

PurposeThe objective of this study was to compare the pharmacokinetics of levofloxacin 1.5% and moxifloxacin hydrochloride 0.5% ophthalmic solutions in aqueous humor after multiple doses prior to cataract surgery.MethodsNinety-eight eyes underwent cataract surgery and met the requirements of PK analysis. Eligible eyes were randomly assigned in a 1:1 ratio to receive levofloxacin or moxifloxacin prior to cataract surgery and were randomized into one of four sampling time points (ie, 1, 2, 4, and 6 hour post-last dose). Randomization was investigator and laboratory-masked. Three days prior to cataract surgery, each patient instilled one drop of the assigned study medication into the operative eye four times daily. One aqueous humor specimen was collected from the eye at the randomized time point. Aqueous humor specimens were assayed for drug concentration using a validated liquid chromatography and tandem mass spectrometer.ResultsConcentrations of the drug in the aqueous humor, as described by mean Cmax and pooled AUC0–6 values, were greater for levofloxacin than moxifloxacin (Cmax: 1.43, 0.87 μg/ml, respectively, P=0.008; AUC0–6 6.1, 3.8 μg·min/ml, P<0.001 respectively). No treatment-emergent adverse events were reported.ConclusionSignificantly greater drug exposures were attained in aqueous humor following the administration of levofloxacin 1.5% than moxifloxacin 0.5% ophthalmic solution. Achieving considerable higher drug concentration in the aqueous humor with levofloxacin 1.5% may demonstrate a greater potential for bacterial eradication.

Increased drug concentration and repeated eye drop administration as strategies to optimize topical drug delivery: A fluorophotometric study in healthy dogs

“…Therefore, we cannot comment on the potential systemic toxicity of the proposed strategies, and we can only speculate that the pharmacological benefits observed in the tear film would translate to clinical benefits in patients with corneal or intraocular pathologies. In humans, a topical fluoroquinolone at 1.5% concentration achieved higher drug levels in the cornea 7 and aqueous humor 7,8 compared with other fluoroquinolones at 0.3–0.5% concentrations. In rabbits, a loading dose of topically applied clarithromycin (i.e., one drop instilled 6 times at 5‐min intervals) provided significantly higher drug levels in the cornea and aqueous humor compared with single antibiotic dosing 28 .…”

“…Drug concentrations in the eye could also be enhanced by increasing drug concentrations in the ophthalmic formulations. In humans, Holland et al 7 showed significantly greater drug concentrations in the cornea (ninefold) and aqueous humor (18‐fold) following topical administration of 1.5% levofloxacin versus 0.3% gatifloxacin, while Bucci et al 8 showed significantly greater aqueous humor concentrations and overall drug exposure (area‐under‐the‐curve) with 1.5% levofloxacin compared with 0.5% moxifloxacin. In both cases, the higher drug concentration of the levofloxacin formulation (1.5% vs. 0.3%–0.5%) played an important role in explaining the study results.…”

Development of topical chitosan/ β-glycerophosphate-based hydrogel loaded with levofloxacin in the treatment of keratitis: An ex-vivo study

“…We selected this drug concentration, based on our previous study, which showed that this drug concentration had a good safety profile [ 45 ]. Many previous studies had examined the levels of drugs in the aqueous humor after the topical application of various levofloxacin concentrations (from 0.5% to 1.5%) in human eyes [ 55 , 56 , 57 ]. Our study was different from those studies in the time points measured and the frequency of drug instillations.…”

Profilaktyka zakażeń po operacji zaćmy: fluorochinolony i leki przeciwzapalne – pojedynczo czy w preparatach złożonych?

“…Moxifloxacin achieved a 3.8 times higher aqueous concentration than gatifloxacin (1.8 ± 1.21 μg/ml vs. 0.48 ± 0.34 μg/ml) and exhibited higher efficacy against Staphylococcus epidermidis [9]. Bucci et al [10] compared the pharmacokinetics of 1.5% levofloxacin and 0.5% moxifloxacin in aqueous humor prior to cataract surgery. The results showed a higher C max (1.43 μg/ml) and area under curve (AUC) dose-response (AUC 0- Authors of the study observed no statistically significant differences in average intraocular pressure at 1 week, 1 month, 3 months and 12 months postoperatively.…”