Ocular pharmacokinetics of subconjunctivally versus intravenously administered 6-mercaptopurine.
The levels of 6-mercaptopurine (6-MP) were measured in the anterior chamber aqueous, the vitreous and the serum of rabbits 0.5, 1, 2, 4, 8 and 12 hours following subconjunctival or intravenous injection of 10 mg/kg in 0.5 mL of saline, the maximum tolerated dose as determined experimentally. The mean peak concentrations of 6-MP in the aqueous and the vitreous respectively of the subconjunctivally injected eyes were 15 and 10 times those achieved in all the eyes following intravenous administration. The bioavailability of the drug over 12 hours was 21.67 micrograms/h in the aqueous and 22.22 micrograms/h in the vitreous following subconjunctival administration but only 1.47 and 3.50 micrograms/h respectively following intravenous administration. The serum concentration of 6-MP following subconjunctival injection was about half that following intravenous administration.
D000042:Absorption; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism*; D001082:Aqueous Humor / Q000378:metabolism; D003229:Conjunctival Diseases / Q000139:chemically induced; D004353:Drug Evaluation, Preclinical; D005123:Eye / Q000378:metabolism*; D005260:Female; D007275:Injections, Intravenous; D007700:Kinetics; D015122:Mercaptopurine / Q000008:administration & dosage / Q000378:metabolism* / Q000633:toxicity; D009883:Ophthalmic Solutions / Q000008:administration & dosage; D011817:Rabbits; D014822:Vitreous Body / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D009883:Ophthalmic Solutions; D015122:Mercaptopurine