Ocular toxicity of intravitreal clarithromycin.
OBJECTIVE
To investigate the ocular toxicity and clearance of intravitreal clarithromycin lactobionate (Klaricid) and to determine the highest nontoxic dose.


METHODS
To evaluate toxicity, 24 New Zealand white rabbits were divided into six groups (four rabbits each). Rabbits were examined preoperatively and electroretinography (ERG) was performed. The left eyes of the animals served as controls and received intravitreal injection of 0.1 mL sterile water. Klaricid (0.1 mL) was injected into the midvitreous cavity of the right eyes at concentrations of 25 microg, 250 microg, 500 microg, 1.0 mg, 2.0 mg, and 4.0 mg/0.1 mL. The animals were followed up to 15 days postinjection by clinical examination and ERG. The animals were killed and the eyes were enucleated and processed for light microscopy. Ten New Zealand rabbits were used for the vitreous clearance study as drug test rabbits and two additional rabbits were used to generate control retina and vitreous. The highest nontoxic dose (1 mg) was injected into the vitreous and the concentration of clarithromycin in the vitreous was determined using high-performance liquid chromatography at various time intervals after injection.


RESULTS
Cataract occurred after intravitreal doses of 2.0 and 4.0 mg. Electroretinography showed decreasing b-wave amplitude with both dark- and light-adapted stimulus in the 4.0-mg group; it was normal in other groups. Histopathologic sections showed localized retinal necrosis and disorganization with the 2.0 and 4.0 mg dosage. No histologic changes were found in the other groups. The half-life of intravitreal clarithromycin was found to be 2 hours. No metabolites of clarithromycin were observed in the vitreous samples.


CONCLUSIONS
Intravitreal clarithromycin lactobionate is nontoxic to rabbit eyes up to a dose of 1.0 mg. Because of its broad-spectrum antibiotic effect and appropriate half-life in the vitreous, it may be a good choice for intravitreal treatment of susceptible organisms.
Unal
M
M
LSU Eye Center, Louisiana State University Medical Center School of Medicine, New Orleans 70112-2234, USA.
Peyman
G A
GA
Liang
C
C
Hegazy
H
H
Molinari
L C
LC
Chen
J
J
Brun
S
S
Tarcha
P J
PJ
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D002386:Cataract / Q000139:chemically induced / Q000473:pathology; D002851:Chromatography, High Pressure Liquid; D017291:Clarithromycin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D003623:Dark Adaptation / Q000187:drug effects; D004195:Disease Models, Animal; D004596:Electroretinography / Q000187:drug effects; D005500:Follow-Up Studies; D006207:Half-Life; D007267:Injections; D009336:Necrosis; D011817:Rabbits; D012160:Retina / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012164:Retinal Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D014822:Vitreous Body / Q000187:drug effects / Q000378:metabolism
D000900:Anti-Bacterial Agents; D017291:Clarithromycin