title: Inoculum effect with chloroquine and Plasmodium falciparum.
abstract: In the studies reported here, we examined the inoculum effect observed with chloroquine and Plasmodium falciparum. The 50% effective doses observed with both chloroquine-susceptible and -resistant parasites increased five- to sevenfold from their baseline values as the inoculum was increased from 2 X 10(5) to 2 X 10(7) parasitized erythrocytes per ml (parasitemias of 0.1 to 10% with a hematocrit of 2%). Increasing the inoculum also decreased the chloroquine uptake per parasitized erythrocyte 15- to 20-fold with both chloroquine-susceptible and -resistant parasites. However, because of the 100-fold increase in the inoculum, the total amount of chloroquine taken up actually increased sufficiently to reduce the extracellular chloroquine concentration in vitro by 60 to 90%. These studies suggest that a chloroquine uptake of greater than or equal to 2.0 pmol/10(6) parasitized erythrocytes is necessary for chloroquine to inhibit parasite growth. More marked reductions in the amount of chloroquine uptake per parasitized erythrocyte were observed with a hematocrit of 40% using similar parasitemias of 0.1 to 10% (inocula of 4 X 10(6) to 4 X 10(8) parasitized erythrocytes per ml). Thin-layer chromatography of [3H]chloroquine taken up by chloroquine-resistant P. falciparum revealed no evidence of drug alteration by the parasite. These studies define the mechanism responsible for the inoculum effect observed with chloroquine and P. falciparum in vitro.
mesh_terms: D000818:Animals; D002738:Chloroquine / Q000378:metabolism / Q000494:pharmacology*; D002855:Chromatography, Thin Layer; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology; D006400:Hematocrit; D006801:Humans; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000378:metabolism
chemical_list: D002738:Chloroquine