Metabolism of chloroquine and hydroxychloroquine in albino and pigmented rats

The administration of chloroquine or hydroxychloroquine to albino and pigmented (hooded) rats at a daily dosage of 40 mg/kg produces a rapid rise in tissue concentrations of the drugs during the first month of medication, but comparatively little further rise when the medications are continued for two additional months. The mean tissue concentration of chloroquine at 1 month is about 100 mg/kg, compared to about 30 mg/kg for hydroxychloroquine. However, rats degrade the latter compound more extensively, so that their total mean tissue content of 4-aminoquinoline bases is greater than 30 mg/kg at that time. The order of increasing tissue concentration for both drugs is almost invariably: muscle, eye, heart, kidney, liver, lung, and spleen. In the pigmented rats, the order is: muscle, heart, kidney, liver, lung, spleen, and eye. When medication is discontinued, the concentrations of both drugs in the tissues decrease very rapidly, except in the eyes of the pigmented rats. Long-continued exposure of the eyes of the pigmented rats to high concentrations (approaching 0.1%) of chloroquine or hydroxychloroquine and their degradation products does not produce any detectable ocular histopathology.