Murine pharmacokinetics of rifapentine delivered as an inhalable dry powder

John G. Y. Chan, Anneliese S. Tyne, Angel Pang, Andrew J. McLachlan, Vidya Perera, Joseph C. Y. Chan, Warwick J. Britton, Hak Kim Chan, Colin C. Duke, Paul M. Young, Daniela Traini

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

A novel inhalable rifapentine dry powder formulation could improve pulmonary rifapentine concentrations resulting in a significantly shorter time to treat tuberculosis infection. The pharmacokinetics of rifapentine (20 mg/kg) in healthy mice was compared following intratracheal (IT) and intraperitoneal (IP) administration. Plasma, bronchoalveolar lavage (BAL) and tissue samples were collected and drug levels were quantified at time points up to 24 h. Concentration–time data were analysed using a mixed-effects modelling approach to provide model-based estimates of area under the concentration–time curve from time 0 to infinity (AUC0–∞). IT delivery had considerably higher peak rifapentine lung and BAL concentrations and associated AUC0–∞ compared with IP delivery. The plasma AUC0–∞ following IT dry powder delivery was ca. four-fold smaller than the value for IP delivery. Inhaled delivery of rifapentine has the potential to selectively enhance therapeutic efficacy at the pulmonary site of infection whilst minimising systemic exposure and related toxicity.
Original languageEnglish
Pages (from-to)319-323
Number of pages5
JournalInternational Journal of Antimicrobial Agents
Volume45
Issue number3
DOIs
Publication statusPublished - 2015
Externally publishedYes

Keywords

  • Tuberculosis
  • Rifapentine
  • Aerosol delivery
  • Inhaled dry powder
  • Granuloma

Fingerprint

Dive into the research topics of 'Murine pharmacokinetics of rifapentine delivered as an inhalable dry powder'. Together they form a unique fingerprint.

Cite this