PQ is metabolized rapidly by both CYP2D6 and MAO. CYP2D6 is known to mediate ring oxidation and demethylation steps, while MAO catalyzes oxidative deamination of the side chain. The effect of 5 µM each of CQ and QN on the generation of known CYP2D6- and MAO-dependent metabolites of 20 µM PQ or its individual enantiomers was assessed using recombinant human enzymes. The influence of the two anti-malarial drugs on the generation of secondary metabolites in human hepatocytes was also investigated. In general, the oxidation of the quinoline ring proved very sensitive to the presence of CQ/QN, whereas the formation of the deaminated products was generally not markedly inhibited. The structures of the major metabolites are presented in Fig. 1.Fig. 1A putative pathway of PQ metabolism in human hepatocytes. Uridine-diphosphate-glucuronic acid which is co-factor necessary for glucuronidation catalyzed by UDPGT (Uridine-diphosphate glucuronosyltransferase); CYP cytochrome P450; ALDH aldehyde dehydrogenase) (First published by Fasinu et al. )