Evidence of microbiome⇓drug interaction between the antimalarial lumefantrine and gut microbiota in mice

Matthew M. Ippolito, Joshua E. Denny, Elizabeth Nenortas, Theresa A. Shapiro, Nathan W. Schmidt

Research output: Contribution to journalArticlepeer-review

Abstract

The antimalarial drug lumefantrine exhibits erratic pharmacokinetics. Intersubject variability might be attributed, in part, to differences in gut microbiome-mediated drug metabolism. We assessed lumefantrine disposition in healthy mice stratified by enterotype to explore associations between the gut microbiota and lumefantrine pharmacokinetics. Gut microbiota enterotypes were classified according to abundance and diversity indices from 16S rRNA sequencing. Pharmacokinetic parameters were computed using noncompartmental analysis. Two distinct enterotypes were identified. Maximal concentration (Cmax) and total drug exposure measured as the area under the drug concentration-time curve (AUC0-24) differed significantly between the groups. The mean and standard deviation of Cmax were 660 ± 220 ng/mL versus 390 ± 59 ng/mL (P = 0.02), and AUC0-24 was 9,600 ± 2,800 versus 5,800 ± 810 ng × h/mL (P = 0.01). In healthy mice intragastrically dosed with the antimalarial drug lumefantrine in combination with artemether, lumefantrine exposure was associated with gut bacterial community structure. Studies of xenobiotic-microbiota interactions can inform drug posology and elucidate mechanisms of drug disposition.

Original languageEnglish (US)
Pages (from-to)1553-1555
Number of pages3
JournalAmerican Journal of Tropical Medicine and Hygiene
Volume103
Issue number4
DOIs
StatePublished - Oct 2020

ASJC Scopus subject areas

  • Parasitology
  • Virology
  • Infectious Diseases

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