Simultaneous assessment of the pharmacokinetics of a pleuromutilin, lefamulin, in plasma, soft tissues and pulmonary epithelial lining fluid

J Antimicrob Chemother. 2016 Apr;71(4):1022-6. doi: 10.1093/jac/dkv442. Epub 2016 Jan 7.


Background: Lefamulin is a pleuromutilin antibiotic under evaluation for the treatment of bacterial infections, including respiratory tract infections. Currently, there are no high-quality pharmacokinetic data on drug tissue concentrations of lefamulin available.

Methods: A single dose of intravenous lefamulin (150 mg) was given to 12 healthy men. The registered EudraCT number for this study was 2010-021938-54. Lefamulin concentrations were simultaneously measured in plasma, skeletal muscle tissue, subcutaneous adipose tissue and epithelial lining fluid (ELF) over 24 h, and corresponding pharmacokinetic parameters were calculated. Microdialysis was used to measure unbound lefamulin concentrations in skeletal muscle tissue and subcutaneous adipose tissue, which were similar to unbound lefamulin concentrations in plasma. Bronchoalveolar lavage was performed 1, 2, 4 and 8 h post-dose to determine lefamulin concentrations in ELF.

Results: Unbound lefamulin levels showed a 5.7-fold higher exposure in ELF compared with that in plasma, demonstrating good penetration to the target site.

Conclusions: Lefamulin may be an addition to the therapeutic armamentarium for the treatment of infections. Simultaneous measurements of unbound drug concentration can guide target attainment for future therapeutic trials.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Infective Agents / administration & dosage
  • Anti-Infective Agents / pharmacokinetics*
  • Diterpenes / administration & dosage
  • Diterpenes / pharmacokinetics
  • Healthy Volunteers
  • Humans
  • Male
  • Microdialysis
  • Polycyclic Compounds
  • Tissue Distribution
  • Young Adult


  • Anti-Infective Agents
  • Diterpenes
  • Polycyclic Compounds
  • pleuromutilin