Figure 2.

Pharmacokinetics and Vulnerable Time-Points for Selection of Partial Resistance. (A) During drug elimination, the unbroken line shows the drug concentration in the blood of a patient who takes the full course of a three-dose drug regimen, which has a long elimination half-life and so its concentration wanes gradually over time. This schematic is based on the antimalarial piperaquine. The window of selection is the time during which drug concentrations are sufficiently high to allow partially resistant parasites to survive, but kill sensitive parasites (in between the horizontal broken lines). During this period, this selection will usually act on parasites from new infections. Above these concentrations (above the upper broken line), both sensitive and partially resistant parasites are killed by the drug, and below these concentrations (below the lower broken line), both sensitive and partially resistant parasites can survive, so there is no selection. The window of selection would be longer for highly resistant parasites compared with parasites with a low level of partial resistance. (B) The red line shows the drug concentration in the blood of a patient who receives a lower than recommended amount of the drug, in this case because they take only one dose instead of three. Drug concentration therefore does not remain at a high enough level for a sufficient length of time to kill all parasites in the initial infection, potentially selecting for partially resistant parasites.