Effects of antacids on the pharmacokinetics of lumefantrine in healthy volunteers: A pilot study.

Abstract

Background: Artemether-lumefantrine (A-L), an artemisinin-based combination therapy (ACT), is a widely used antimalarial drug and it could be prescribed together with antacids since malaria may co-exist with peptic ulcer. This study aimed to determine possible interaction following concurrent administration of A-L and commonly used antacids, and to monitor possible corrected-QT (QTc) interval prolongation. Methods: In a randomized crossover study, single oral dose of A-L (80/480 mg) tablet alone or in combination with antacid formulation (magnesium trisilicate, magnesium carbonate, sodium bicarbonate combination) were administered to 13 healthy volunteers after overnight fast. Blood samples were collected at predetermined time intervals and plasma samples for six volunteers were successfully assayed for lumefantrine using High performance Liquid Chromatography (HPLC). Electrocardiographic recording was carried out at predetermined times. Results: The median lumefantrine AUC0-96 of 173 µg.hr/ml (IQR: 72.11-688.51) and 221.96 µg.hr/ml (IQR: 64.21-465.47) were obtained when A-L was taken alone and in combination with antacid formulation respectively. The median lumefantrine Cmax for A-L alone and for A-L plus antacid formulation were 5.92 µg/ml (IQR: 2.08-14.44) and 4.42 µg/ml (IQR: 3.84-14.30) respectively. The mean QTc intervals obtained at pre-dose, 6-, 72- and 504-hours post-dose were 390.08±19.84,406.23±19.04, 394.60±19.91 and 396.33±23.94 ms respectively. The lengthening of the QTc interval at 6 hr post-dose compared to zero (0) hr was statistically significant (P<0.05). Conclusion: In this preliminary study, antacids did not appear to alter the reported erratic bioavailability of lumefantrine in human. Also, the limited increase in QTc interval caused by lumefantrine was not clinically significant.