Purchase this article with an account.
C. Civiale, A. Blanco, F. Giuliano, E. Mattei, M.G. Mazzone; New Fixed Netilmicin/Dexamethasone Combination: in vitro and in vivo Preclinical Studies . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2605.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
The aim of this work was to investigate the in vivo ocular distribution of a new steroid–antibiotic combination and the possible functional interference between the actives in vitro. The fixed combination contains 0.132% dexamethasone phosphate equal to dexamethasone alcohol 0.1%(DEX) and 0.455% netilmicin sulphate equal to netlmicin base 0.3% (NET).
A) In vivo: 50µl of the steroid–antibiotic combination were instilled (single dose) into the eye of New Zealand albino rabbits. Cornea, conjunctiva and aqueous humour were collected at different time points and processed to determine the concentrations of NET and DEX by using HPLC/fluorescence or LC/MS–MS, respectively. B) In vitro: the possible interference of DEX on NET anti–bacterial activity was assessed using the minimum inhibitory concentrations (MICs) of NET either alone or in the presence of 0.1% DEX. Conversely, the potential interference of 0.3% NET on DEX activity was evaluated by measuring inhibition of nitrite accumulation in a LPS–stimulated murine cell line (J774.2).
Pharmacokinetic results are displayed in the table below.
MIC values obtained for NET alone did not differ from those obtained in the presence of DEX. The concentration of NET in the conjunctiva was found above MIC values for S. aureus and S. epidermidis up to 12 hours post dose. With regard to E. coli and P. aeruginosa NET concentrations above MIC were reached in the conjunctiva 2 hours after administration and maintained for the following 2 hours. DEX effectively inhibited the LPS–induced accumulation of nitrite in a similar fashion both in the absence and in the presence of NET.
The anti–inflammatory and antimicrobial activities of DEX and NET are maintained in the fixed combination. The promising pharmacokinetic profiles observed after a single administration suggests that in the clinical setting this new steroid–antibiotic combination will be able to treat external ocular inflammations in the presence or suspect of bacterial infection.
This PDF is available to Subscribers Only