Chloroquine - How It Works

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.

Cardiac Electrophysiology QTc interval prolongation was studied in a randomized, placebo-controlled parallel trial in 116 healthy subjects who received either chloroquine (1,000 mg) alone or in combination with oral azithromycin (500 mg, 1,000 mg, and 1,500 mg once daily).

Co-administration of azithromycin increased the QTc interval in a dose- and concentration- dependent manner.

In comparison to chloroquine alone, the maximum mean (95% upper confidence bound) increases in QTcF were 5 ms, 7 ms and 9 ms with the co-administration of 500 mg, 1,000 mg and 1,500 mg azithromycin, respectively.

Microbiology Mechanism of Action: Chloroquine, a 4-aminoquinoline, is an anti-protozoal agent.

The precise mechanism by which chloroquine exhibits activity is not known.

Chloroquine, may exert its effect against Plasmodium species by concentrating in the acid vesicles of the parasite and by inhibiting polymerization of heme.

It can also inhibit certain enzymes by its interaction with DNA.

Activity in Vitro and in Clinical Infections: Chloroquine is active against the erythrocytic forms of susceptible strains of Plasmodium falciparum, Plasmodium malariae , Plasmodium ovale, and Plasmodium vivax .

Chloroquine is not active against the gametocytes and the exoerythrocytic forms including the hypnozoite stage ( P. vivax and P. ovale ) of the Plasmodium parasites.

In vitro studies with Chloroquine demonstrated that it is active against the trophozoites of Entamoeba histolytica.

Drug Resistance: Resistance of Plasmodium parasites to chloroquine is widespread (see INDICATIONS AND USAGE , Limitations of Use in Malaria and WARNINGS ).