1921
Volume 103, Issue 4
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645
USD
Buy:$15.00

Abstract

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 ( ) and total drug exposure measured as the area under the drug concentration–time curve (AUC) differed significantly between the groups. The mean and standard deviation of were 660 ± 220 ng/mL versus 390 ± 59 ng/mL ( = 0.02), and AUC was 9,600 ± 2,800 versus 5,800 ± 810 ng × h/mL ( = 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.

Loading

Article metrics loading...

The graphs shown below represent data from March 2017
/content/journals/10.4269/ajtmh.20-0333
2020-07-06
2020-10-31
Loading full text...

Full text loading...

http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.20-0333
Loading
/content/journals/10.4269/ajtmh.20-0333
Loading

Data & Media loading...

  • Received : 22 Apr 2020
  • Accepted : 28 May 2020
  • Published online : 06 Jul 2020
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error