Norimichi Akiyama1, Naoki Inui1,2, Kazutaka Mori1, Yutaro Nakamura1, Hiroshi Hayakawa3, Shimako Tanaka4, Shinya Uchida4, Noriyuki Namiki4, Hiroshi Watanabe2, Takafumi Suda1. 1. Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Handayama, Hamamatsu, Japan. 2. Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, Handayama, Hamamatsu, Japan. 3. Department of Respiratory Medicine, Tenryu Hospital, Oro, Hamamatsu, Japan. 4. Department of Pharmacy Practice and Science, School of Pharmaceutical Sciences University of Shizuoka, Shizuoka, Japan.
Abstract
BACKGROUND: The prevalence of pulmonary infections caused by nontuberculous mycobacteria (NTM) is increasing worldwide. Furthermore, the treatment of infections caused by the Mycobacterium avium-intracellulare complex (MAC) remains challenging. The cytochrome P450 (CYP) enzyme inducer, rifampicin, and the CYP inhibitor, clarithromycin, have clinical activity against MAC and key drugs in the treatment of MAC infection. The interaction of rifampicin and clarithromycin may influence the therapeutic process. METHODS: Thirty-one Japanese chemo-naïve patients with pulmonary MAC infection were included in the study. Before and after 7-day administration of rifampicin and clarithromycin, the pharmacokinetics of midazolam, a CYP3A-specific probe, were analyzed. The concentrations of midazolam were determined by liquid chromatography-tandem mass spectrometry. None of the patients were receiving any other medications that might affect CYP3A activity. RESULTS: Of the patients, 24 (77.4%) were infected with Mycobacterium avium (M. avium) and 7 (22.6%) were infected with Mycobacterium intracellulare (M. intracellulare). The concentrations of midazolam were significantly reduced with administration of rifampicin and clarithromycin [the median (range) was 1.75 (0.70-8.22) to 1.04 (0.30-2.63) ng/mL, P<0.0001]. The differences in midazolam levels were not correlated with clinical characteristics. CONCLUSIONS: Coadministration of rifampicin and clarithromycin may increase CYP3A enzymatic activity. 2019 Journal of Thoracic Disease. All rights reserved.
BACKGROUND: The prevalence of pulmonary infections caused by nontuberculous mycobacteria (NTM) is increasing worldwide. Furthermore, the treatment of infections caused by the Mycobacterium avium-intracellulare complex (MAC) remains challenging. The cytochrome P450 (CYP) enzyme inducer, rifampicin, and the CYP inhibitor, clarithromycin, have clinical activity against MAC and key drugs in the treatment of MAC infection. The interaction of rifampicin and clarithromycin may influence the therapeutic process. METHODS: Thirty-one Japanese chemo-naïve patients with pulmonary MAC infection were included in the study. Before and after 7-day administration of rifampicin and clarithromycin, the pharmacokinetics of midazolam, a CYP3A-specific probe, were analyzed. The concentrations of midazolam were determined by liquid chromatography-tandem mass spectrometry. None of the patients were receiving any other medications that might affect CYP3A activity. RESULTS: Of the patients, 24 (77.4%) were infected with Mycobacterium avium (M. avium) and 7 (22.6%) were infected with Mycobacterium intracellulare (M. intracellulare). The concentrations of midazolam were significantly reduced with administration of rifampicin and clarithromycin [the median (range) was 1.75 (0.70-8.22) to 1.04 (0.30-2.63) ng/mL, P<0.0001]. The differences in midazolam levels were not correlated with clinical characteristics. CONCLUSIONS: Coadministration of rifampicin and clarithromycin may increase CYP3A enzymatic activity. 2019 Journal of Thoracic Disease. All rights reserved.
Authors: David E Griffith; Timothy Aksamit; Barbara A Brown-Elliott; Antonino Catanzaro; Charles Daley; Fred Gordin; Steven M Holland; Robert Horsburgh; Gwen Huitt; Michael F Iademarco; Michael Iseman; Kenneth Olivier; Stephen Ruoss; C Fordham von Reyn; Richard J Wallace; Kevin Winthrop Journal: Am J Respir Crit Care Med Date: 2007-02-15 Impact factor: 21.405
Authors: Jennifer Adjemian; Kenneth N Olivier; Amy E Seitz; Steven M Holland; D Rebecca Prevots Journal: Am J Respir Crit Care Med Date: 2012-02-03 Impact factor: 21.405
Authors: Jakko van Ingen; Eric F Egelund; Adrah Levin; Sarah E Totten; Martin J Boeree; Johan W Mouton; Rob E Aarnoutse; Leonid B Heifets; Charles A Peloquin; Charles L Daley Journal: Am J Respir Crit Care Med Date: 2012-06-28 Impact factor: 21.405
Authors: J Christopher Gorski; Suda Vannaprasaht; Mitchell A Hamman; Walter T Ambrosius; Melissa A Bruce; Barbara Haehner-Daniels; Stephen D Hall Journal: Clin Pharmacol Ther Date: 2003-09 Impact factor: 6.875
Authors: Isabel H Gonzalez-Bocco; Muneerah M Aleissa; Eric Zhou; Jennifer Manne-Goehler; Sophia Koo; Matthew P Cheng; Francisco M Marty Journal: Open Forum Infect Dis Date: 2021-12-18 Impact factor: 3.835