Reversal of Drug-Resistant Falciparum Malaria by Calcium Antagonists: Potentialfor Host Cell Toxicity

摘要

Agents capable of reversing multidrug resistance (mdr) in falciparum malaria wereinvestigated for potentiation of chloroquine accumulation and toxicity in a cell culture system. Verapamil, its analog R011-2933, and desipramine caused a dose-dependent increase in the accumulation of chloroquine (CQ) within human and mouse hepatocytes but not human lung cells. Only those cells in which drug accumulation was enhanced by reversing agents reacted positively for P-glycoprotein (PgP)-the putative mediator of the enhanced drug efflux characteristic of mdr. (jes)