Paper: Daraprim—Clinical trials and pharmacology

Abstract

Field trails have indicated the relatively high efficacy of Daraprim in controlling parasitemia in man following infection with Plasmodium vivax and P. falciparum. No toxic after-effects from the use of the drug could be detected at the level of doses used. Its preatest value may be as a suppressant and also in mass prophylaxis. The action of the drug is much slower than is the case for chloroquine when used for treatment of acute infections and should not be utilized for that purpose under normal conditions. The pharmacology of the drug shows that doses far above the therapeutic level are necessary before damage to mammalian tissue appears. Such damage seems to be connected with a type of antimetabolitic action against the folic acid series of vitamins which are necessary in normal cell division. This interference is most noticeable in the formation of new blood cells. Since plasmodial cell division components are attacked in the same manner, their far greater sensitivity to the drug enables its use at concentrations far below the critical level for mammalian tissue systems. Sera from people treated with Daraprim show an antifolic activity lasting several days and thus may indicate the actual formation of an active metabolite of Daraprim origin. The drug is tasteless and is readily taken by children. It is the only antimalarial drug thus far developed which has this particular characteristic.