Lansoprazole-sulfide, pharmacokinetics of this promising anti-tuberculous agent

Biomed Chromatogr. 2017 Dec;31(12). doi: 10.1002/bmc.4035. Epub 2017 Jul 13.


Lansoprazole (LPZ) is a commercially available proton-pump inhibitor whose primary metabolite, lansoprazole sulfide (LPZS) was recently reported to have in vitro and in vivo activity against Mycobacterium tuberculosis. It was also reported that a 300 mg kg-1 oral administration of LPZS was necessary to reach therapeutic levels in the lung, with the equivalent human dose being unrealistic. A validated liquid chromatography-tandem mass spectrometric method (LC-MS/MS) for the simultaneous quantification LPZ and LPZS in rat plasma and lung homogenates was developed. We administered 15 mg kg-1 oral doses of LPZ to a healthy rat model to determine the pharmacokinetics of its active metabolite, LPZS, in plasma and lung tissue. We found that the LPZS was present in amounts that were below the limit of quantification. This prompted us to administer the same dose of LPZS to the experimental animals intraperitoneally (i.p.). Using this approach, we found high concentrations of LPZS in plasma and lung, 7841.1 and 9761.2 ng mL-1 , respectively, which were significantly greater than the minimum inhibitory concentration (MIC) for Mycobacterium tuberculosis. While oral and i.p. administration of LPZ resulted in significant concentrations in the lung, it did not undergo sufficient cellular conversion to its anti-TB metabolite. However, when LPZS itself was administered i.p., significant amounts penetrated the tissue. These results have implications for future in vivo studies exploring the potential of LPZS as an anti-TB compound.

Keywords: LC-MS/MS; Mycobacterium tuberculosis; lansoprazole sulfide; pharmacokinetics.

MeSH terms

  • Administration, Oral
  • Animals
  • Antitubercular Agents / administration & dosage
  • Antitubercular Agents / analysis*
  • Antitubercular Agents / chemistry
  • Antitubercular Agents / pharmacokinetics*
  • Chromatography, Liquid / methods
  • Female
  • Lansoprazole / administration & dosage
  • Lansoprazole / analysis*
  • Lansoprazole / chemistry
  • Lansoprazole / pharmacokinetics*
  • Linear Models
  • Lung / chemistry
  • Lung / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Tandem Mass Spectrometry / methods


  • Antitubercular Agents
  • Lansoprazole