A study of the phototoxic potential of trovafloxacin in BALB/c mice.
Trovafloxacin, a broad-spectrum naphthyridone antimicrobial agent, was evaluated for potential phototoxicity in a standardized in-vivo test system that has been used previously to assess quinolone antibiotics. Fasted BALB/c mice were given a single oral dose of either trovafloxacin mesylate (10, 30, 90 or 250 mg/kg) or the positive control lomefloxacin hydrochloride (71 mg/kg) and immediately exposed to long-wave ultraviolet (UVA) light. Animals were irradiated for 4 h, equal to a total UV light irradiation of approximately 18 J/cm2. Before dosing, at the end of the irradiation period and at approximately 24, 48, 72 and 96 h after dosing, both ears of each mouse were evaluated for changes indicative of a positive response: erythema, oedema or a measurable increase in ear thickness. Under the conditions of this study, trovafloxacin produced a mild response (erythema and a slight increase in ear thickness) in mice given a dose of 90 or 250 mg/kg; no significant response was observed in mice given either lower doses (10 or 30 mg/kg) or the vehicle. In contrast, 71 mg/kg of lomefloxacin produced a strong and persistent phototoxic response. The results of this study demonstrate that the phototoxic potential of trovafloxacin is considerably less than that of lomefloxacin and, when compared with similar studies with related compounds, suggest that trovafloxacin is among the least phototoxic of the fluoroquinolone class.
Mayne
J T
JT
Central Research Division, Pfizer Inc., Groton, CT 06340, USA.
Johnson
N J
NJ
Kluwe
W M
WM
Lencoski
D L
DL
Polzer
R J
RJ
D000818:Animals; D000890:Anti-Infective Agents / Q000032:analysis / Q000097:blood / Q000633:toxicity*; D017484:Dermatitis, Phototoxic / Q000209:etiology*; D004890:Erythema / Q000139:chemically induced; D005260:Female; D024841:Fluoroquinolones; D006984:Hypertrophy / Q000139:chemically induced; D051379:Mice; D008807:Mice, Inbred BALB C; D009287:Naphthyridines / Q000032:analysis / Q000097:blood / Q000633:toxicity*; D015363:Quinolones / Q000633:toxicity; D012867:Skin / Q000737:chemistry / Q000187:drug effects / Q000528:radiation effects; D014466:Ultraviolet Rays
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D009287:Naphthyridines; D015363:Quinolones; C080163:trovafloxacin; C053091:lomefloxacin