Cytotoxicity of five fluoroquinolone and two nonsteroidal anti-inflammatory benzalkonium chloride-free ophthalmic solutions in four corneoconjunctival cell lines

Figures & data

Table 1 Antibiotic ophthalmic solutions evaluated in the present study

Active component	Trade name	Preservative	CVS50*
Levofloxacin (0.5%)	Cravit (Santen, Osaka, Japan) Quixin (in US; Vistakon, Jacksonville, FL, USA; with 0.005% BAK)	No	3
Moxifloxacin (0.5%)	Vigamox (Alcon, Fort Worth, TX, USA)	No	1
Gatifloxacin (0.3%)	Gatiflo (Senju, Osaka, Japan) Zymar (in US; Allergan, Irvine, CA, USA; with 0.005% BAK)	No	2
Norfloxacin (0.3%)	Noflo (Banyu, Tokyo, Japan)	No	2
Tosufloxacin (0.3%)	Tosuflo (Nitto, Nagoya, Japan)	No	3
Dibekacin (0.5%)	Panimycin (Meiji, Tokyo, Japan)	No	3
Cefmenoxime (0.5%)	Bestron (Kaken, Tokyo, Japan)	0.026% methyl paraoxybenzoate, 0.014% propyl paraoxybenzoate, boric acid	4

Notes:

* Number of cell lines with viability ≥50% in the presence of a 10-fold dilution of the drug.

Abbreviation: BAK, benzalkonium chloride.

Figure 1 Effects of antibiotic ophthalmic solutions on the viability of cultured rabbit corneal epithelial cells (RC-1 and SIRC), bovine corneal epithelial cells (BCE), and human conjunctival cells (Chang) after 48 h exposure. Data are the mean ± SD. Cefmenoxime was the least toxic. The cell viability score was determined and the order of cell viability was cefmenoxime ≥ tosufloxicin ≥ dibekacin ≥ levofloxacin ≥ norfloxacin = gatifloxacin = moxifloxacin (Table 1).

Figure 2 Effects of anti-inflammatory ophthalmic solutions on the viability of cultured rabbit corneal epithelial cells (RC-1 and SIRC), bovine corneal epithelial cells (BCE), and human conjunctival cells (Chang) after 48 h exposure. Data are the mean ± SD. Data for benzalkonium chloride (BAK)-free drugs are indicated by the dotted lines. Cell viability was greater in all BAK-free solutions, except for Diclod, compared with solutions containing BAK. The cell viability score was determined and the order of viability was betamethasone ≥ betamethasone + fradiomycin > preservative-free diclofenac ≥ preservative-free bromfenac >> 0.02% fluoromethorone ≥ 0.1% fluoromethorone = diclofenac + preservative (Diclod) = bromfenac + preservative (Bronuck) = pranoprofen.

Table 2 Anti-inflammatory ophthalmic solutions evaluated in the present study

Active component	Trade name	Preservative	CVS50*
Betamethasone (0.1%)	Rinderon (Shinogi, Osaka, Japan)	0.05% methyl paraoxybenzoate, 0.02% propyl paraoxybenzoate	4
Betamethasone (0.1%) + fradiomycin (0.35%)	Rinderon A (Shionogi)	Same as Rinderon	4
Fluoromethorone (0.1%)	Flumethoron 0.1% (Santen, Osaka, Japan)	0.005% BAK, polysorbate 80,	0
Fluoromethorone (0.02%)	Flumethoron 0.02% (Santen)	0.005% BAK, polysorbate 80	0
Diclofenac (0.1%)	Diclod (Wakamoto, Tokyo, Japan) Voltaren Ophthalmic Solution (in US; Novartis, East Hanover, NJ, USA)	Chlorobutanol, polysorbate 80, boric acid	0
Preservative-free diclofenac	No brand name (experimental use only)	No	1
Bromfenac (0.1%)	Bronuck (Senju, Osaka, Japan) Xibrom (in US; ISTA Pharmaceuticals, Irvine, CA, USA)	0.005% BAK, polysorbate 80	0
Preservative-free bromfenac	No brand name (experimental use only)	No	3
Pranoprofen (0.1%)	Niflan (Senju)	0.007% BAK, polysorbate 80, boric acid	0

Notes:

* Number of cell lines with viability ≥50% in the presence of a 10-fold dilution of the drug.

Abbreviation: BAK, benzalkonium chloride.

Figure 3 Effects of preservatives on the viability of cultured rabbit corneal epithelial cells (RC-1 and SIRC), bovine corneal epithelial cells (BCE), and human conjunctival cells (Chang) after 48 h exposure. Data are the mean ± SD. Benzalkonium chloride and polysorbate were shown to have dose-dependent cytotoxic effects.