Pharmacokinetics of Meropenem for Use in Bacterial Keratitis

Investigative Ophthalmology & Visual Science
Henri SuekeTimothy Neal

Abstract

To investigate the toxicity and corneal pharmacokinetics of meropenem as a potential antimicrobial for bacterial keratitis. Corneal epithelial cell and keratocyte toxicity was investigated using methyl thiazolyl tetrazolium (MTT) and LIVE/DEAD assays. The penetration of meropenem through the human cornea was measured using an artificial anterior chamber. In one group of corneas, the epithelial and endothelial layers were removed and in a second group these layers were left intact. We applied 50 μL (10 mg/mL) meropenem to the corneal surface and collected samples in the anterior chamber from 45 minutes up to 24 hours. Meropenem concentrations were estimated with a bioassay and HPLC. Meropenem had significantly higher cellular metabolic activity (MTT assay) at both 5 mg/mL and 2.5 mg/mL compared with moxifloxacin (P = 0.029 and P = 0.018, respectively), with 96% cell viability (LIVE/DEAD assay). The measured values for meropenem concentrations in corneal and aqueous samples were significantly higher using a bioassay than with HPLC (P = 0.004). For both intact and denuded corneas, the concentrations in the anterior chamber increased from 0.48 μg/mL (SD 0.89) and 0.89 μg/mL (SD 0.81) to 6.35 μg/mL (SD 0.81) and 13.48 μg/mL (SD 14.8...Continue Reading

Citations

Mar 30, 2016·Journal of Pharmaceutical Sciences·Sie Huey LeeReginald B H Tan
Jan 19, 2021·The Biochemical Journal·Daniel M FoulkesStephen B Kaye
Nov 17, 2020·Eye & Contact Lens·Erdinç BozkurtSeyit Ali Bingol
Aug 11, 2021·Nature Communications·Danielle J IngleDeborah A Williamson

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