Aqueous humour concentrations after topical apPlication of combinEd levofloxacin-dexamethasone eye dRops and of its single components: a randoMised, assEssor-blinded, parallel-group study in patients undergoing cataract surgery: the iPERME study

Michele Figus, Chiara Posarelli, Dario Romano, Marco Nardi, Luca Rossetti, Michele Figus, Chiara Posarelli, Dario Romano, Marco Nardi, Luca Rossetti

Abstract

Purpose: To 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.

Methods: Randomised, 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.

Results: A 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.

Conclusion: Our 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 registration: ClinicalTrials.gov Identifier: NCT03740659.

Keywords: Aqueous humour; Combination eye drop; Dexamethasone; Levofloxacin.

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Study design
Fig. 2
Fig. 2
AH concentrations of levofloxacin (top) and of dexamethasone (bottom) after ocular instillation of levofloxacin + dexamethasone sodium phosphate (LDSP), levofloxacin (L) or dexamethasone sodium phosphate (DSP). See doses in the text. Data are means ± SD; Nobs = number of observations

References

    1. Barry P, Cordovés L, Gardner S ESCRS Guidelines for prevention and treatment of endophthalmitis following cataract surgery: data, dilemmas and conclusions 2013. . last accessed 7 Sept 2019
    1. Behndig A, Cochener B, Guell JL, et al. Endophthalmitis prophylaxis in cataract surgery: overview of current practice patterns in 9 European countries. J Cataract Refract Surg. 2013;39:1421–1431. doi: 10.1016/j.jcrs.2013.06.014.
    1. Chang DF, Braga-Mele R, Handerson BA, Mamalis N, Vasavada A, ASCRS Cataract Clinical Commitee Antibiotic prophylaxis of postoperative endophthalmitis after cataract surgery: results of the 2014 ASCRS member survey. J Cataract Refract Surg. 2015;41(6):1300–1305. doi: 10.1016/j.jcrs.2015.01.014.
    1. Cagini C, Cometa F, Torroni G, Pellegrino A, Pellegrino R, Cavallini GM. Dexamethasone disodium phosphate penetration in to the human aqueous humour after topical application. Curr Eye Res. 2016;41(7):897–899. doi: 10.3109/02713683.2015.1083589.
    1. Bucci FA. An in vivo study comparing the ocular absorption of levofloxacin and ciprofloxacin prior to phacoemulsification. Am J Ophthalmol. 2004;137:308–312. doi: 10.1016/j.ajo.2003.08.057.
    1. Healy DP, Holland EJ, Nordlund ML, Dunn S, Chow C, Lindstrom RL, Hardten D, Davis E. Concentrations of levofloxacin, ofloxacin, and ciprofloxacin in human corneal stromal tissue and aqueous humour alter topical administration. Cornea. 2004;23:255–263. doi: 10.1097/00003226-200404000-00007.
    1. Puustjarvi T, Terasvirta M, Nurmenniemi P, et al. Penetration of topically applied levofloxacin 0.5% and ofloxacin 0.3% into the vitreous of the non-inflamed human eye. Graefes Arch Clin Exp Ophthalmol. 2006;244:1633–1637. doi: 10.1007/s00417-006-0360-0.
    1. Yamada M, Mochizuki H, Yamada K, et al. Aqueous humour levels of topically applied levofloxacin in human eyes. Curr Eye Res. 2002;24:403–406. doi: 10.1076/ceyr.24.5.403.8517.
    1. Rosenblum C, Dengler RE, Jr, Geoffroy RF. Ocular absorption of dexamethasone phosphate disodium by the rabbit. Arch Ophthalmol. 1967;77(2):234–237. doi: 10.1001/archopht.1967.00980020236017.
    1. Fan S, Guo T, Chen B et al (2019) Differences in ocular biometrics and aqueous humour dynamics between Chinese and Caucasian adults. Br J Ophthalmol 20
    1. Yamaguchi K, Ohno A, Ishii Y, Tateda K, Iwata M, Levofloxacin-Surveillance Group In vitro susceptibilities to levofloxacin and various antibacterial agents of 12,866 clinical isolates obtained from 72 centers in 2010. Jpn J Antibiot. 2012;65(3):181–206.
    1. Bucci FA, Jr, Nguimfack IT, Fluet AT. Pharmacokinetics and aqueous humor penetration of levofloxacin 1.5% and moxifloxacin 0.5% in patients undergoing cataract surgery. Clin Ophthalmol. 2016;10:783–789. doi: 10.2147/OPTH.S91286.
    1. Wejitens O, Schoemaker RC, Romijn FP, et al. Intraocular penetration and systemic absorption after topical application of dexamethasone disodium phosphate. Ophthalmology. 2002;109(10):1887–1891. doi: 10.1016/S0161-6420(02)01176-4.
    1. Decadron - Riassunto delle caratteristiche del prodotto (SmPC) Italy, from AIFA website . Accessed 31 Mar 2020
    1. Berezhkovskiy LM. Prediction of drug terminal half-life and terminal volume of distribution after intravenous dosing based on drug clearance, steady-state volume of distribution, and physiological parameters of the body. J Pharm Sci. 2013;102(2):761–771. doi: 10.1002/jps.23396.
    1. Spoorenberg SM, Deneer VH, Grutters JC, Pulles AE, Voorn GP, Rijkers GT, Bos WJ, van de Garde EM. Pharmacokinetics of oral vs. intravenous dexamethasone in patients hospitalized with community-acquired pneumonia. Br J Clin Pharmacol. 2014;78(1):78–83. doi: 10.1111/bcp.12295.
    1. Coassin M, Bandello F Medical treatment after cataract surgery: evidence for a new anti-inflammatory strategy. Proc. 37th Congress of the ESCRS, Paris, 2019, FP-297744

Source: PubMed

Спонсоры и соавторы

Заболевания

Медикаментозные вмешательства

Подписаться