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 mumol/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 > or = 10.4 mumol/L. With 48 and 72 h of exposure, the inhibition lasted for 6-8 d at concentrations > or = 1.3 mumol/L and for 8-11 d at concentrations between 2.6 and 166 mumol/L. After 96 h of exposure, parasites were inhibited for 11-17 d at concentrations > or = 0.65 mumol/L. With 168 h of exposure, parasites were inhibited at all quinine concentrations > or = 0.65 mumol/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 mumol/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.