Parasitology: A requiem for chloroquine

Science

Volumn 298, Issue 5591, 2002, Pages 74-75

  Hastings, I M ^a   Bray, P G ^a   Ward, S A ^a  

^a LIVERPOOL SCHOOL OF TROPICAL MEDICINE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ARTESUNATE; CHLOROQUINE; FANSIDAR; GENE PRODUCT; PROTEIN PFCRT; UNCLASSIFIED DRUG;

PARASITOLOGY;

AFRICA; CROSS RESISTANCE; GENE EXPRESSION REGULATION; GENE MUTATION; GENETIC RECOMBINATION; HAPLOTYPE; MALARIA; MORTALITY; PLASMODIUM FALCIPARUM; PRIORITY JOURNAL; SHORT SURVEY;

ANIMALS; ANTIMALARIALS; ARTEMISININS; CHLOROQUINE; DRUG RESISTANCE; DRUG THERAPY, COMBINATION; DRUG TOLERANCE; EVOLUTION, MOLECULAR; GENES, PROTOZOAN; HUMANS; MALARIA, FALCIPARUM; MEMBRANE PROTEINS; MUTATION; PLASMODIUM FALCIPARUM; PROTOZOAN PROTEINS; SESQUITERPENES; TETRAHYDROFOLATE DEHYDROGENASE;

PLASMODIUM FALCIPARUM;

EID: 0037020208     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.1077573     Document Type: Short Survey

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11. A subtherapeutic CQ level is defined as a concentration permissive for a fully sensitive parasite, emerging from the liver stage, to establish a viable infection. CQ has a long terminal elimination half-life, enabling it to be detected weeks after ingestion, but its persistence at therapeutic levels is short because the circulating free CQ concentrations achieved post-distribution (after clinical dosing) rapidly fall below that required to kill or exert selective pressure against the parasite. Therapeutic concentrations must be maintained for 6 or 7 days to consistently achieve parasite clearance, but it seems unlikely that CQ therapeutic levels are maintained much beyond this point. The authors used 10 days based on an informed guess, although the qualitative argument remains unchanged even if this period is extended up to 20 days.