Abstract
PurposeTo evaluate the penetration of levofloxacin and dexamethasone sodium phosphate into the aqueous humour (AH) after administration in combination and as single molecules. Evaluation of the penetration of those agents in the site of action and their pharmacodynamic potential activity in view of the intended clinical use after cataract surgery.MethodsRandomised, assessor-blinded, parallel-group. Patients scheduled for cataract surgery were assigned in a 1:1:1 ratio to: levofloxacin + dexamethasone sodium phosphate (L-DSP), Levofloxacin (L) or Dexamethasone sodium phosphate (DSP) eye drops. Either test or reference drugs were instilled in the cul-de-sac twice, 90 and 60 min before paracentesis.ResultsA total of 125 patients completed the study. Fraction of dose absorbed in the anterior chamber was 3.8–4.2 · 10−4 for levofloxacin and 0.3–0.4 · 10−4 for dexamethasone, respectively. No notable differences in concentration of levofloxacin were found between L-DSP arm (1.970 nmol/ml) and L arm (2.151 nmol/ml). The concentrations of levofloxacin were well above the MICs for the most frequent Gram-positive and Gram-negative eye pathogens. Dexamethasone concentrations were slightly lower in L-DSP arm (0.030 nmol/ml) than in DSP arm (0.042 nmol/ml), but still in the pharmacodynamically active range in the site of action. The difference was not clinically relevant. DSP was not detected in any HA sample, suggesting its full hydrolysis to free dexamethasone.ConclusionOur results confirm that no interaction is evident on the corneal penetration of levofloxacin and dexamethasone which reach pharmacologically active concentrations when instilled as fixed combination eye drops to patients undergoing cataract surgery.Trial registrationClinicalTrials.gov Identifier: NCT03740659
Highlights
Postoperative endophthalmitis is an inflammatory condition of the eye, due to an infectious process from bacteria, fungiElectronic supplementary material The online version of this article contains supplementary material, which is available to authorized users.The prophylaxis of postoperative bacterial ocular infections such as endophthalmitis consists in the administration of intraocular, usually intracameral or subconjunctival antibiotics during surgery
The samples were retested, and the one previously containing 0.014 nmol/ml no longer presented trace of levofloxacin. – Dexamethasone average concentration was 0.030 nmol/ ml (95% CI (0.025; 0.035)) in the levofloxacin + dexamethasone sodium phosphate (L-Dexamethasone sodium phosphate (DSP)) group (corresponding to 11.774 ng/ml) and 0.042 nmol/ml (95% CI (0.035; 0.048)) in the DSP group (corresponding to 16.483 ng/ml)
The combination of dexamethasone sodium phosphate, corresponding to dexamethasone 1 mg/ml, plus levofloxacin 5 mg/ml (L-DSP) tested in this study is the first combination of a steroid and levofloxacin under development as eye drops
Summary
Postoperative endophthalmitis is an inflammatory condition of the eye, due to an infectious process from bacteria, fungi. The prophylaxis of postoperative bacterial ocular infections such as endophthalmitis consists in the administration of intraocular, usually intracameral or subconjunctival antibiotics during surgery. Both pre- and postoperative topical applications are used frequently [2]. A broad-spectrum antibiotic is indicated, and topical use of quinolones may represent a rational choice given their bactericidal activity against both the gram-positive and gram-negative bacteria most frequently responsible for bacterial eye infections. Postoperative care after cataract surgery consists of topical anti-inflammatory and antibacterial drug prophylaxis. Eye Drop Combi (L-DSP) is a fixed dose combination (FDC) of eye drops solution, with 0.5% levofloxacin and 0.132% dexamethasone sodium phosphate (corresponding to 0.1% free dexamethasone) as active ingredients, under development by NTC Srl, Milan (Italy)
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