Pharmacokinetics and allometric scaling of antimalarial drugs

Abstract

Allometric scaling was found as a plausible technique for dose determination in children. Permeability and P-glycoprotein efflux transport of antimalarials were determined using in-vitro Caco-2 cells. Mefloquine showed P-glycoprotein inhibition. Amodiaquine, artesunate and artemisone were not P-glycoprotein substrates or inhibitors. Methylene-blue showed some P-glycoprotein mediated efflux. Permeability was high for amodiaquine and artemisone, medium for mefloquine and artesunate and low for methylene-blue. P-glycoprotein was up-regulated when exposed to dihydroartemisinin/artemisone in combinations with amodiaquine/mefloquine.