CLINICAL PHARMACOLOGY
Chloroquine is rapidly and almost completely absorbed from the gastrointestinal tract, and only a small proportion of the administered dose is found in the stools. Approximately 55% of the drug in the plasma is bound to nondiffusible plasma constituents. Excretion of chloroquine is quite slow, but is increased by acidification of the urine. Chloroquine is deposited in the tissues in considerable amounts. In animals, from 200 to 700 times the plasma concentration may be found in the liver, spleen, kidney, and lung; leukocytes also concentrate the drug. The brain and spinal cord, in contrast, contain only 10 to 30 times the amount present in plasma.
Chloroquine undergoes appreciable degradation in the body. The main metabolite is desethylchloroquine, which accounts for one fourth of the total material appearing in the urine; bisdesethylchloroquine, a carboxylic acid derivative, and other metabolic products as yet uncharacterized are found in small amounts. Slightly more than half of the urinary drug products can be accounted for as unchanged chloroquine.
Microbiology
Mechanism of Action
Chloroquine is an antimalarial agent. While the drug can inhibit certain enzymes, its effect is believed to result, at least in part, from its interaction with DNA. However, the mechanism of plasmodicidal action of chloroquine is not completely certain.
Activity in vitro and in vivo
Chloroquine is active against the erythrocytic forms of Plasmodium vivax. Plasmodium malariae, and susceptible strains of Plasmodium falciparum (but not the gametocytes of P. falciparum). It is not effective against exoerythrocytic forms of the parasite.
In vitro studies with trophozoites of Entamoeba histolytica have demonstrated that chloroquine also possesses amebicidal activity comparable to that of emetine.
Drug Resistance
Resistance of Plasmodium falciparum to chloroquine is widespread and cases of Plasmodium vivax resistance have been reported.
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