Rifapentine is a semi-synthetic, long-acting rifamycin antibiotic. Rifapentine binds to the beta subunit of bacterial DNA-dependent RNA polymerase, thereby blocking the transcription process and exerting its bactericidal effect by inhibiting bacterial RNA synthesis. Rifapentine can be used in the research and treatment of tuberculosis (such as active pulmonary tuberculosis and latent tuberculosis infection), leprosy, and other infections caused by susceptible bacteria[1-4].
In vitro, Rifapentine (2.5μM) and Vincristine (5nM) were used to treat P-gp-overexpressing drug-resistant KBV20C cancer cells for 48 hours. Rifapentine significantly increased cytotoxicity but did not exhibit significant P-gp inhibitory activity[5]. Rifapentine (0.001-10μg/mL) was used to pretreat the human monocytic leukemia cell line (THP-1), followed by infection with the virulent NMI strain. Rifapentine significantly inhibited bacterial growth[6].
In vivo, administered via gavage either before or after infection, Rifapentine (20mg/kg/day) was given to wild-type and immunodeficient Yellow fever virus (YFV)-infected mice for 21 days. Rifapentine significantly improved the survival rate, alleviated clinical signs, and reduced the viral load and degree of injury in target organs[7]. Rifapentine (10mg/kg; once weekly) alone or in combination with Isoniazid and other drugs was administered to Swiss mice infected with Mycobacterium tuberculosis (M. tuberculosis H37Rv) for 6 months. Rifapentine monotherapy failed to clear the bacteria from the mouse lungs and selected for rifampicin-resistant mutants; the combination therapy with Moxifloxacin and other drugs significantly suppressed the lung bacterial load and reduced the relapse rate after discontinuation[8].
References:
[1] Sharma SK, Sharma A, Kadhiravan T, et al. Rifamycins (rifampicin, rifabutin and rifapentine) compared to isoniazid for preventing tuberculosis in HIV-negative people at risk of active TB. Cochrane Database Syst Rev. 2013 Jul 5;2013(7):CD007545.
[2] Klemens SP, Cynamon MH. Activity of rifapentine against Mycobacterium avium infection in beige mice. J Antimicrob Chemother. 1992 May;29(5):555-61.
[3] Albano M, Karau MJ, Greenwood-Quaintance KE, et al. In Vitro Activity of Rifampin, Rifabutin, Rifapentine, and Rifaximin against Planktonic and Biofilm States of Staphylococci Isolated from Periprosthetic Joint Infection. Antimicrob Agents Chemother. 2019 Oct 22;63(11):e00959-19.
[4] Rifat D, Prideaux B, Savic RM, et al. Pharmacokinetics of rifapentine and rifampin in a rabbit model of tuberculosis and correlation with clinical trial data. Sci Transl Med. 2018 Apr 4;10(435):eaai7786.
[5] Lee JS, Oh Y, Kim HS, et al. Low-Dose Rifabutin Increases Cytotoxicity in Antimitotic-Drug-Treated Resistant Cancer Cells by Exhibiting Strong P-gp-Inhibitory Activity. Int J Mol Sci. 2022 Jul 2;23(13):7383.
[6] Miller HK, Kersh GJ. Efficacy of rifapentine and other rifamycins against Coxiella burnetii in vitro. Microbiol Spectr. 2024 Jul 2;12(7):e0103424.
[7] Qian X, Wu B, Tang H, et al. Rifapentine is an entry and replication inhibitor against yellow fever virus both in vitro and in vivo. Emerg Microbes Infect. 2022 Dec;11(1):873-884.
[8] Lounis N, Bentoucha A, Truffot-Pernot C, et al. Effectiveness of once-weekly rifapentine and moxifloxacin regimens against Mycobacterium tuberculosis in mice. Antimicrob Agents Chemother. 2001 Dec;45(12):3482-6.