Resum
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 390.0819.84, 406.2319.04, 394.6019.91 and 396.3323.94 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.
Keywords: Artemether-lumefantrine, QTc interval, antacids, antimalarial, drug interaction.
Résumé
Contexte: L’artéméther-luméfantrine (A-L), une association thérapeutique à base d’artémisinine (ACT), est un médicament antipaludique largement utilisé qui peut être prescrit avec des antiacides, car le paludisme peut coexister avec l’ulcère peptique. Cette étude visait à déterminer l’interaction possible après l’administration concomitante d’A-L et d’antiacides couramment utilisés, et à surveiller l’allongement possible de l’intervalle QT corrigé (QTc).
Méthodes: Dans une étude croisée randomisée, une dose orale unique de comprimé A-L (80/480 mg) seul ou en combinaison avec une formulation antiacide (trisilicate de magnésium, carbonate de magnésium, bicarbonate de sodium) a été administrée à 13 volontaires sains après une nuit de jeûne. Des échantillons de sang ont été recueillis à des intervalles de temps prédéterminés et des échantillons de plasma pour six volontaires ont été testés avec succès pour la luméfantrine en utilisant une Chromatographie liquide à haute performance (HPLC). L’enregistrement électrocardiographique a été effectué à des moments prédéterminés.
Résultats: LaluméfantrinemédianeAUC0-96de 173μg.hr / ml (IQR: 72,11-688,51) et221,96 μg.hr / ml(IQR: 64,21- 465,47) ont été obtenues lorsque l’A-Létait prise seule et en combinaison avec la formulation antiacide respectivement. La luméfantrine médianeCmaxpour A-L seul et pour A-L + formulation antiacide étaient 5,92μg / ml (IQR: 2,08- 14,44) et4,42μg / ml (IQR: 3,84-14,30) respectivement. Lesintervalles QTcmoyens obtenus avant administration de la dose, 6, 72 et 504 heures après administrationétaient de 390,08 19,84;406,2319,04; 394,6019,91 et 396,3323,94 ms respectivement.L’allongement de l’intervalleQTc à 6heurespost-doseparrapport à zéro (0)hétait statistiquement significative (P0<05).
Conclusion: Dans cette étude préliminaire, les antiacides ne semblent pas modifier la biodisponibilité erratique de la luméfantrine chez les humains. De plus, l’augmentation limitée de l’intervalle QTc causée par la luméfantrine n’était pas cliniquement significative.
Mots- clés: artéméther-luméfantrine, intervalle QTc, antiacides, antipaludéen, interaction médicamenteuse
Correspondence: Prof. Chinedum P. Babalola, Department of Pharmaceutical Chemistry, University of Ibadan, Ibadan, Nigeria. E-mail: peacebab@gmail.com
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