Characterising blood stage antimalarial drug minimum inhibitory concentrations in vivo using reinfection patterns [PublishAheadOfPrint]

The minimum inhibitory concentration (MIC) is an essential quantitative measure of the asexual blood stage effect of an antimalarial drug. In areas of high malaria transmission, and thus frequent individual infection, patients who are treated with slowly eliminated antimalarials become reinfected as drug concentrations decline. In the frequent relapse forms of P. vivax and in P. ovale malaria, recurrent infection occurs from relapses which begin to emerge from the liver approximately two weeks after the primary illness. An important determinant of the interval from starting treatment of a symptomatic infection to the patency of these recurrent infections is the in vivo concentration-response relationship and thus the in vivo MIC. Using mechanistic knowledge of parasite asexual replication and the pharmacokinetic and pharmacodynamic properties of the antimalarial drugs, a generative statistical model was derived which relates the concentration-response relationship to time of reinfection patency. This model was used to estimate the in vivo MIC of chloroquine in the treatment of Plasmodium vivax malaria.

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