The potential mechanisms underlying these interactions are unknown at present, but could be presumptively metabolism-linked. Until recently, the focus on PQ metabolites in clinical studies has been towards carboxy-primaquine (CPQ), which has been reported to be the major circulating metabolite . In one study conducted to investigate interactions among anti-malarial drugs, QN caused a decrease in the area under the curve (AUC0–24h) of CPQ by about 50 % . More recently, Pukrittayakamee et al.  conducted an open-label, cross-over, pharmacokinetic interaction study in 16 health human subjects. Volunteers received single doses of 30 mg PQ, 600 mg CQ, or the combination thereof. In contrast to the QN results, CQ caused a significant increase in the plasma levels of both PQ and its major metabolite, CPQ. Thus, these two drugs, while sharing a beneficial effect on PQ efficacy and toxicity, apparently do so by affecting mechanisms other than the monoamine oxidase-mediated metabolism of PQ to CPQ. Other pathways of PQ metabolism, now known to be prominent in human liver—but so far difficult to pinpoint their ultimate disposition—have not been explored from the perspective of CQ and QN effects.