Skip to content
DraconiticResearch
Search Sources API
197,768 studies31 sourcesUpdated 57 min ago
Peer-reviewedCC BY 4.0Antimicrobial Agents and Chemotherapy

Pulmonary pharmacokinetics and lesion penetration of antimicrobials in patients with nontuberculous mycobacterial disease

  • Fumiya Watanabe1,2
  • Miyako Hiramatsu3
  • Toru Kawakami4
  • Teruaki Oka5
  • Hayato Nanami3
  • Kiyomi Shimoda3
  • Kazuhiko Hanada1
  • Yuji Shiraishi3
  • Kozo Morimoto6,7,8
8 affiliations
  1. 1Department of Pharmacometrics and Pharmacokinetics, Meiji Pharmaceutical University, Tokyo, Japan
  2. 2Department of Pharmacy, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan
  3. 3Department of Thoracic Surgery, Respiratory Disease Center, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan
  4. 4Department of Thoracic Surgery, Higashi-yamato Hospital, Tokyo, Japan
  5. 5Department of Pathology, Respiratory Disease Center, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan
  6. 6Department of Respiratory Medicine, Respiratory Disease Centre, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan
  7. 7Department of Clinical Research, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan
  8. 8Department of Clinical Mycobacteriosis, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
Read full textDOICite

Abstract

The intrapulmonary pharmacokinetics of antimicrobial agents used to treat nontuberculous mycobacterial (NTM) pulmonary disease remains poorly characterized, limiting the optimization of dosing regimens. This study characterized the plasma and intrapulmonary pharmacokinetics of azithromycin, ethambutol, rifampicin, clofazimine, and amikacin, as well as their penetration into pulmonary lesion sites. We prospectively enrolled patients undergoing guideline-based treatment for NTM pulmonary disease who were indicated for surgical resection at a single center in Japan. Drug concentrations were measured in the plasma and lung samples and analyzed using a population pharmacokinetic model. The lung lesion site, cavity, or nodule/bronchiectatic lesion was evaluated as covariates of the lung-to-plasma partition ratios. Twenty-four patients were enrolled in the study. The estimated lung-to-plasma partition coefficients and intrapulmonary half-lives were 535-fold and 6.3 months for azithromycin, 40-fold and 2.0 months for ethambutol, 5.2-fold and 6.3 min for rifampicin, 18,800-fold and 22 years for clofazimine, 1.3-fold and 2.3 h for intravenous amikacin, and 1.3-fold and 5.0 h for inhaled amikacin, respectively. Evaluation of drug penetration into cavities and nodular/bronchiectatic lesions showed no clearly reduced concentration compared to a normal lung tissue. The intrapulmonary pharmacokinetic characteristics identified in this study provide valuable information for optimizing antimicrobial dosing regimens in the treatment of NTM pulmonary disease. Furthermore, the absence of clearly reduced drug penetration into lesion sites suggests that lesion phenotype alone may have limited value in guiding antimicrobial selection.

Related

  1. Asymptomatic Tattoo-Associated Cutaneous Nontuberculous Mycobacterial Infection: Case Report.
    Chris Alihosseini, Milana Stein, Ana Sofia Acosta Madiedo +3
    JMIR dermatologyPeer-reviewedCC BYFull textInfectious diseaseEurope PMCPMCDOAJ
  2. Falling short: Inadequate target attainment in guideline-based therapy of nontuberculous mycobacterial disease
    T. J. Shoaf, T. Dierckman, N. Strawhacker +7
    medRxivPreprintCC BYFull textInfectious diseasemedRxiv
  3. Imipenem and relebactam pharmacokinetics in peritoneal fluid: microdialysis reveals infection-independent penetration
    Huan Tong, Zekun Cao, Jiakai Li +5
    Antimicrobial Agents and ChemotherapyPeer-reviewedCC BY 4.0Full textPharmacology & toxicologyPMC
  4. Efficacy outcomes in non-tuberculous mycobacterial pulmonary disease studies: a scoping review
    Siwei Gu, Xiaojing Cui, Mengwei Yan +2
    TrialsPeer-reviewedCC BY-NC-ND 4.0Epidemiology & public healthCrossref
  5. Notes from the Field: Nontuberculous Mycobacteria Infections After Cosmetic Surgery Procedures in Mexico - United States, April-September 2025.
    Neel Swamy, Michelle Sandoval-Rosario, Dumbani Kayira +20
    MMWR. Morbidity and mortality weekly reportPeer-reviewedLicence not statedFull textEpidemiology & public healthEurope PMC

Cite

BibTeXRIS
BibTeX
@article{watanabe2026pulmonary,
  title = {{Pulmonary pharmacokinetics and lesion penetration of antimicrobials in patients with nontuberculous mycobacterial disease}},
  author = {Fumiya Watanabe and Miyako Hiramatsu and Toru Kawakami and Teruaki Oka and Hayato Nanami and Kiyomi Shimoda and Kazuhiko Hanada and Yuji Shiraishi and Kozo Morimoto},
  journal = {Antimicrobial Agents and Chemotherapy},
  year = {2026},
  month = oct,
  doi = {10.1128/aac.00820-26},
  url = {https://doi.org/10.1128/aac.00820-26},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Pulmonary pharmacokinetics and lesion penetration of antimicrobials in patients with nontuberculous mycobacterial disease
AU  - Fumiya Watanabe
AU  - Miyako Hiramatsu
AU  - Toru Kawakami
AU  - Teruaki Oka
AU  - Hayato Nanami
AU  - Kiyomi Shimoda
AU  - Kazuhiko Hanada
AU  - Yuji Shiraishi
AU  - Kozo Morimoto
PY  - 2026
DA  - 2026/10/01
JO  - Antimicrobial Agents and Chemotherapy
DO  - 10.1128/aac.00820-26
UR  - https://doi.org/10.1128/aac.00820-26
AB  - The intrapulmonary pharmacokinetics of antimicrobial agents used to treat nontuberculous mycobacterial (NTM) pulmonary disease remains poorly characterized, limiting the optimization of dosing regimens. This study characterized the plasma and intrapulmonary pharmacokinetics of azithromycin, ethambutol, rifampicin, clofazimine, and amikacin, as well as their penetration into pulmonary lesion sites. We prospectively enrolled patients undergoing guideline-based treatment for NTM pulmonary disease who were indicated for surgical resection at a single center in Japan. Drug concentrations were measured in the plasma and lung samples and analyzed using a population pharmacokinetic model. The lung lesion site, cavity, or nodule/bronchiectatic lesion was evaluated as covariates of the lung-to-plasma partition ratios. Twenty-four patients were enrolled in the study. The estimated lung-to-plasma partition coefficients and intrapulmonary half-lives were 535-fold and 6.3 months for azithromycin, 40-fold and 2.0 months for ethambutol, 5.2-fold and 6.3 min for rifampicin, 18,800-fold and 22 years for clofazimine, 1.3-fold and 2.3 h for intravenous amikacin, and 1.3-fold and 5.0 h for inhaled amikacin, respectively. Evaluation of drug penetration into cavities and nodular/bronchiectatic lesions showed no clearly reduced concentration compared to a normal lung tissue. The intrapulmonary pharmacokinetic characteristics identified in this study provide valuable information for optimizing antimicrobial dosing regimens in the treatment of NTM pulmonary disease. Furthermore, the absence of clearly reduced drug penetration into lesion sites suggests that lesion phenotype alone may have limited value in guiding antimicrobial selection.
SN  - 0066-4804
SN  - 1098-6596
ER  -