Publication: Drug interactions between dolutegravir and artemether-lumefantrine or artesunate-amodiaquine
Issued Date
2019-02-01
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ISSN
10986596
00664804
00664804
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2-s2.0-85060798453
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Mahidol University
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SCOPUS
Bibliographic Citation
Antimicrobial Agents and Chemotherapy. Vol.63, No.2 (2019)
Suggested Citation
Stephen I. Walimbwa, Mohammed Lamorde, Catriona Waitt, Julian Kaboggoza, Laura Else, Pauline Byakika-Kibwika, Alieu Amara, Joshua Gini, Markus Winterberg, Justin Chiong, Joel Tarning, Saye H. Khoo Drug interactions between dolutegravir and artemether-lumefantrine or artesunate-amodiaquine. Antimicrobial Agents and Chemotherapy. Vol.63, No.2 (2019). doi:10.1128/AAC.01310-18 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/51917
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Drug interactions between dolutegravir and artemether-lumefantrine or artesunate-amodiaquine
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Abstract
© 2019 Walimbwa et al. Across sub-Saharan Africa, patients with HIV on antiretrovirals often get malaria and need cotreatment with artemisinin-containing therapies. We undertook two pharmacokinetic studies in healthy volunteers, using standard adult doses of artemether-lumefantrine or artesunate-amodiaquine given with 50 mg once daily dolutegravir (DTG) to investigate the drug-drug interaction between artemether-lumefantrine or artesunate-amodiaquine and dolutegravir. The dolutegravir/artemether-lumefantrine interaction was evaluated in a two-way crossover study and measured artemether, dihydroartemisinin, lumefantrine, and desbutyl-lumefantrine over 264 h. The dolutegravir/artesunate-amodiaquine interaction was investigated using a parallel study design due to long half-life of the amodiaquine metabolite, desethylamodiaquine and measured artesunate, amodiaquine, and desethylamodiaquine over 624 h. Noncompartmental analysis was performed, and geometric mean ratios and 90% confidence intervals were generated for evaluation of both interactions. Dolutegravir did not significantly change the maximum concentration in plasma, the time to maximum concentration, and the area under the concentration-time curve (AUC) for artemether, dihydroartemisinin, lumefantrine, and desbutyl-lumefantrine, nor did it significantly alter the AUC for artesunate, dihydroartemisinin, amodiaquine, and desethylamodiaquine. Coadministration of dolutegravir with artemether-lumefantrine resulted in a 37% decrease in DTG trough concentrations. Coadministration of dolutegravir with artesunate-amodiaquine resulted in 42 and 24% approximate decreases in the DTG trough concentrations and the AUC, respectively. The significant decreases in DTG trough concentrations with artemether-lumefantrine and artesunate-amodiaquine and dolutegravir exposure with artesunate-amodiaquine are unlikely to be of clinical significance since the DTG trough concentrations were above dolutegravir target concentrations of 300 ng/ml. Study drugs were well tolerated with no serious adverse events. Standard doses of artemether-lumefantrine and artesunate-amodiaquine should be used in patients receiving dolutegravir.