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AIDS:
doi: 10.1097/QAD.0b013e32835cae3b
Clinical Science: Concise Communications

Lower artemether, dihydroartemisinin and lumefantrine concentrations during rifampicin-based tuberculosis treatment

Lamorde, Mohammeda,b; Byakika-Kibwika, Paulinea,b,c; Mayito, Jonathana; Nabukeera, Lilliana; Ryan, Mairinb; Hanpithakpong, Waruneed; Lefèvre, Gilberte; Back, David J.f; Khoo, Saye H.f; Merry, Conceptaa,b,g

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Abstract

Objective: To investigate the pharmacokinetics of artemether, dihydroartemisinin and lumefantrine during rifampicin intake and after stopping rifampicin.

Study design: An open-label, two-phase, longitudinal drug interaction study with patients serving as their own controls.

Methods: We recruited HIV-1-seropositive Ugandan adults who were receiving rifampicin-based tuberculosis treatment and who did not have malaria. Pharmacokinetic sampling after six doses of artemether-lumefantrine was performed during rifampicin-based tuberculosis treatment (phase 1) and repeated at least 3 weeks after stopping rifampicin-based tuberculosis treatment (phase 2).

Results: Six and five patients completed phases 1 and 2, respectively. Median age and weight were 30 years and 64 kg. Artemether and dihydroartemisinin area under the concentration–time curve (AUC0–12h) were significantly lower by 89% [geometric mean ratio (GMR) 90% confidence interval (CI) 0.11, 0.05–0.26] and 85% (0.15, 0.10–0.23), respectively, during rifampicin-based treatment when compared to AUC0–12h after stopping rifampicin intake. Similarly, artemether and dihydroartemisinin Cmax were 83% (0.17, 0.08–0.39) and 78% (0.22, 0.15–0.33) lower, respectively, during rifampicin treatment. For artemether, mean (±SD) C12 was 0.5(±1.0) and 5.9(±2.5) ng/ml in phases 1 and 2, respectively. Corresponding values for dihydroartemisinin (DHA) were 0.3(±0.4) and 4.7(±2.0) ng/ml, respectively. Day 8 lumefantrine concentration was significantly lower by 84% (GMR 90% CI 0.16, 0.09–0.27), and AUCDay3-Day25 was significantly lower by 68% (GMR 90% CI 0.32, 0.21–0.49) during rifampicin-based treatment when compared to exposure values after stopping rifampicin.

Conclusion: Pharmacokinetic parameters for artemether-lumefantrine were markedly lower during rifampicin-based tuberculosis treatment. Artemether-lumefantrine should not be co-administered with rifampicin.

© 2013 Lippincott Williams & Wilkins, Inc.

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