Animal toxicity and pharmacokinetics of hydroxychloroquine sulfate

Chloroquine is two to three times as toxic in animals as hydroxychloroquine, even though various single and repeated oral dosage regimens in man have given nearly identical plasma level curves. Tissue distributions are qualitatively similar for both drugs in albino rats--namely, bone, fat, and brain less than muscle less than eye less than heart less than kidney less than liver less than lung less than spleen less than adrenal--but the absolute distribution values are about 2.5 times higher for chloroquine. The metabolism of chloroquine and hydroxychloroquine differs only in that the latter drug gives two first-stage metabolites, whereas chloroquine gives one. Oral absorption of both drugs in man is nearly complete. However, three times as much chloroquine as hydroxychloroquine appears in the urine, and three times as much hydroxychloroquine as chloroquine appears in the feces.