SUSCEPTIBILITY OF PLASMODIUM-FALCIPARUM TO QUININE IN-VITRO - EFFECTS OF DRUG CONCENTRATIONS AND TIME OF EXPOSURE

We have studied the relationship between quinine concentrations ranging from 0.16 to 332 mu mol/L in a blood-medium mixture and the time of exposure (12-168 h) needed for inhibition of Plasmodium falciparum (F32 strain) in continuous culture. When we exposed the parasites for 12 h, only brief inhibition was observed. After 24 h of exposure, parasites were inhibited for 2-3 d at quinine concentrations greater than or equal to 10.4 mu mol/L. With 48 and 72 h of exposure, the inhibition lasted for 6-8 d at concentrations greater than or equal to 1.3 mu mol/L and for 8-11 d at concentrations between 2.6 and 166 mu mol/L. After 96 h of exposure, parasites were inhibited for 11-17 d at concentrations greater than or equal to 0.65 mu mol/L. With 168 h of exposure, parasites were inhibited at all quinine concentrations greater than or equal to 0.65 mu mol/L during 28 d of post-exposure cultivation. After reappearance, parasites multiplied on average 7.6 fold during each parasite schizogony cycle. The calculated parasite elimination rate in the presence of effective concentrations of quinine was 99.7-99.9% per cycle. We conclude that the elimination rate of the parasites is concentration-dependent at low concentrations of quinine in vitro. As soon as a threshold concentration of 0.65-2.6 mu mol/L is attained, only the exposure time determines parasite elimination. These experiments suggest that it might be preferable to reduce each dose rather than the duration of treatment in areas where P. falciparum is susceptible to quinine.