Subconjunctival versus intravenous cytosine arabinoside: effect of route of administration and ocular toxicity.

The ocular penetration, elimination, and toxicity of equidose cytosine arabinoside (Ara-C) (37.5 mg/kg) following subconjunctival versus intravenous injection were compared in rabbits. Drug levels were measured at 0.5, 1, 2, 4, 8, and 12 hours in serum, urine, and ocular compartments. Following subconjunctival administration, the peak concentration of Ara-C in the anterior chamber was 15 times and in the vitreous twice that obtained following intravenous administration. Drug levels obtained were considered high enough to be effective in inhibiting the growth of selected tumor lines. The cumulative urinary excretion over 12 hours was 67% and 70% for the subconjunctivally and intravenously injected animals, respectively, and peak serum levels were 0.061 mM and 0.170 mM, respectively. Clinical and histologic toxicity following subconjunctival injection was minimal, and no bone marrow suppression was detected at the dose level administered.