Quinine is extensively metabolized by CYP3A4 to an active metabolite, 3-hydroxyquinine. Quinine and it metabolites are also glucuronidated with up to 60% of the administered dose excreted as urinary glucuronides and ~20–25% excreted as unchanged quinine. Coadministration of single doses of quinine (600 mg, single dose) with lopinavir/ritonavir (400/100 mg, twice daily) in two studies decreased quinine AUC and Cmax by 56% and 47%, and by 50% and 48%; 3-hydroxyquinine AUC and Cmax by 99% and 85% in the first study and both decreased by 69% in the second study. No significant effects on lopinavir or ritonavir AUC and Cmax were seen in either study. Coadministration raises concerns of suboptimal exposure of the antimalarial treatment. However, since the free concentration of quinine was increased in both studies, further investigations are wanted to determine the clinical significance of this interaction and decide whether dosage adjustments are needed. In addition, caution is advised when prescribing lopinavir/ritonavir and medicinal products known to induce QT interval prolongation such as quinine (prolongation of the QT interval, widening of the QRS complex and T wave flattening has been noted with therapeutic doses of quinine).