title: On the mechanism for the red-cell accumulation of mefloquine, an antimalarial drug.
abstract: The accumulation of the antimalarial drug mefloquine by human red blood cells has been studied by 19F-NMR spectroscopy. The uptake process was nonlinearly dependent on the external drug concentration. Concentrations inside cells as high as 60-times greater than those in the extracellular phosphate-buffered-saline were observed. Red-cell ghosts were also found to accumulate mefloquine with high-affinity binding sites for the drug. Hemoglobin was found to bind mefloquine with low affinity, but due to the high concentration of this protein it is a significant drug compartment in the red cell. Analysis of the 19F-NMR chemical shifts and linewidths of mefloquine in the presence of red cells, red-cells ghosts and hemoglobin indicates restricted mobility of the drug in the membrane-bound state and slow exchange with the extracellular medium. This is a significant characteristic of the reaction in connection with the prophylactic activity of the drug. Exchange of the drug between hemoglobin and the red-cell membrane, however, is fast and may play an important role in the bioavailability of the drug to the parasite.
mesh_terms: D000962:Antimalarials / Q000097:blood*; D001692:Biological Transport; D004910:Erythrocyte Membrane / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D015767:Mefloquine; D011804:Quinolines / Q000097:blood*
chemical_list: D000962:Antimalarials; D011804:Quinolines; D015767:Mefloquine