Progress in the application of rifabutin in tuberculosis comorbidities

doi:10.19871/j.cnki.xfcrbzz.2025.04.013

Abstract

Abstract: Rifabutin, an essential derivative of rifamycin, occupies a significant position in anti-infection treatment due to its strong cell membrane penetration, broad-spectrum antibacterial activity, and exceptional antibacterial efficacy. Although its use currently focuses mainly on treating Mycobacterium avium complex (MAC) and other non-tuberculous mycobacteria (NTM) infections, its potential for addressing comorbidities of tuberculosis is gradually gaining attention, particularly in complex combination therapy scenarios. Its low enzyme induction effect considerably reduces drug interactions with other medications, ensuring the safety and effectiveness of treatment. This article systematically reviews the pharmacological characteristics of rifabutin, explores its antibacterial activity and interaction mechanisms with other drugs, and summarizes its clinical value in treating comorbidities of tuberculosis. Clinical evidence has shown that rifabutin has good efficacy and tolerability for a variety of tuberculosis comorbidities, such as AIDS, hypertension, and diabetes. In addition, this article summarizes the possible adverse effects of rifabutin in clinical application to provide a reference for clinicians when selecting treatment options.

Key words: Rifabutin, Rifamycin, Tuberculosis, Comorbidities, Drug interactions

CLC Number:

He Mingjie, Xu Rong, Deng Guofang. Progress in the application of rifabutin in tuberculosis comorbidities[J]. Electronic Journal of Emerging Infectious Diseases, 2025, 10(4): 76-82.

References

[1] WORLD HEALTH ORGANIZATION. Global tuberculosis report2024[EB/OL]. [2024-10-29]. https://www.who.int/ publications/i/item/9789240101531.
[2] SURETTE MD, SPANOGIANNOPOULOS P, WRIGHT GD.The Enzymes of the Rifamycin Antibiotic Resistome[J]. Acc Chem Res, 2021, 54(9): 2065-2075.
[3] BORRACCINO AV, CELIBERTO F, PRICCI M, et al.Rifabutin as salvage therapy for Helicobacter pylori eradication: Cornerstones and novelties[J]. World J Gastroenterol, 2022, 28(45): 6356-6362.
[4] NILLES J, THEILE D, WEISS J, et al.Lack of CYP3A4 protein induction despite mRNA induction in primary hepatocytes exposed to rifabutin as a possible explanation for its low interaction risk in vivo[J]. Arch Toxicol, 2024, 98(8): 2541-2556.
[5] KIM M, JOHNSON CE, SCHMALSTIG AA, et al.A long-acting formulation of rifabutin is effective for prevention and treatment of Mycobacterium tuberculosis[J]. Nat Commun, 2022, 13(1): 4455.
[6] TREBOSC V, KEMMER C, LOCIURO S, et al.Rifabutin for infusion (BV100) for the treatment of severe carbapenem-resistant Acinetobacter baumannii infections[J]. Drug Discov Today, 2021, 26(9): 2099-2104.
[7] BURMAN WJ, GALLICANO K, PELOQUIN C.Comparative pharmacokinetics and pharmacodynamics of the rifamycin antibacterials[J]. Clin Pharmacokinet, 2001, 40(5): 327-341.
[8] BOORGULA GD, JAKKULA L, GUMBO T, et al.Comparison of Rifamycins for Efficacy Against Mycobacterium avium Complex and Resistance Emergence in the Hollow Fiber Model System[J]. Front Pharmacol, 2021, 12: 645264.
[9] BRAINARD DM, KASSAHUN K, WENNING LA, et al.Lack of a clinically meaningful pharmacokinetic effect of rifabutin on raltegravir: in vitro/in vivo correlation[J]. J Clin Pharmacol, 2011, 51(6): 943-950.
[10] MADADI AK, SOHN MJ.Comprehensive Therapeutic Approaches to Tuberculous Meningitis: Pharmacokinetics, Combined Dosing, and Advanced Intrathecal Therapies[J]. Pharmaceutics, 2024, 16(4).
[11] 林立敏, 叶寒辉. 利福霉素类药物治疗结核病的临床应用研究进展[J]. 药物评价研究, 2020, 43(11): 5.
[12] LE X, GUO X, SUN J, et al.Pharmacokinetic features of dolutegravir with rifampicin and rifabutin among patients coinfected with human immunodeficiency virus and tuberculosis/mycobacterium avium complex[J]. Int J Infect Dis, 2022, 116: 147-150.
[13] 中华医学会感染病学分会艾滋病丙型肝炎学组, 中国疾病预防控制中心. 中国艾滋病诊疗指南(2021年版)[J]. 协和医学杂志, 2022, 13(02): 203-226.
[14] ROCKWOOD N, CERRONE M, BARBER M, et al.Global access of rifabutin for the treatment of tuberculosis - why should we prioritize this?[J]. J Int AIDS Soc, 2019, 22(7): e25333.
[15] 方木通, 苏优峰, 毛智, 等. GeneXpert MTB/RIF检测利福平耐药结核分枝杆菌的表型药物敏感试验耐药情况[J]. 中国防痨杂志, 2021, 43: 1159-1163.
[16] NIRBHAVANE P, VEMURI N, KUMAR N, et al.Lipid Nanocarrier-Mediated Drug Delivery System to Enhance the Oral Bioavailability of Rifabutin[J]. AAPS PharmSciTech, 2017, 18(3): 829-837.
[17] CRABOL Y, CATHERINOT E, VEZIRIS N, et al.Rifabutin: where do we stand in 2016?[J]. J Antimicrob Chemother, 2016, 71(7): 1759-1771.
[18] WALLIS RS, GOOD CE, O'RIORDAN MA, et al. Mycobactericidal activity of bedaquiline plus rifabutin or rifampin in ex vivo whole blood cultures of healthy volunteers: A randomized controlled trial[J]. PLoS One, 2018, 13(5): e0196756.
[19] GUGNANI JS, ABHISHEK F, AGARWAL Y, et al.Effectiveness of Rifabutin-Based Regimens in Treating Helicobacter pylori Infections[J]. Cureus, 2023, 15(12): e50541.
[20] LEE SS, MEINTJES G, KAMARULZAMAN A, et al.Management of tuberculosis and latent tuberculosis infection in human immunodeficiency virus-infected persons[J]. Respirology, 2013, 18(6): 912-922.
[21] 丁志鹏. 利福布汀联合含依非韦伦或克力芝抗病毒方案治疗艾滋病合并结核病的效果分析[J]. 基层医学论坛, 2021, 25: 3754-3755.
[22] KAWUMA AN, WASMANN RE, DOOLEY KE, et al.Drug-drug interaction between rifabutin and dolutegravir: A population pharmacokinetic model[J]. Br J Clin Pharmacol, 2023, 89(3): 1216-1221.
[23] YOGESH S, NALLATHAMBI N, GANAPATHY RK, et al.Assessing the Effect of the Anti-tuberculosis Drug Rifampicin on Known Hypertensive Patients With Tuberculosis in a Tertiary Care Center[J]. Cureus, 2023, 15(11): e49701.
[24] LEE SL, LIM WJ, CHAI ST.Resistant hypertension during antituberculosis treatment: how is rifampicin implicated?[J]. Med J Malaysia, 2020, 75(5): 591-593.
[25] TAYLOR AA, SIRAGY H, NESBITT S.Angiotensin receptor blockers: pharmacology, efficacy, and safety[J]. J Clin Hypertens (Greenwich), 2011, 13(9): 677-686.
[26] LIU W, YAN T, CHEN K, et al.Predicting Interactions between Rifampin and Antihypertensive Drugs Using the Biopharmaceutics Drug Disposition Classification System[J]. Pharmacotherapy, 2020, 40(4): 274-290.
[27] VAN CREVEL R, KOESOEMADINATA R, HILL PC, et al.Clinical management of combined tuberculosis and diabetes[J]. Int J Tuberc Lung Dis, 2018, 22(12): 1404-1410.
[28] AL-BARI MAA, PEAKE N, EID N.Tuberculosis-diabetes comorbidities: Mechanistic insights for clinical considerations and treatment challenges[J]. World J Diabetes, 2024, 15(5): 853-866.
[29] CáCERES G, CALDERON R, UGARTE-GIL C. Tuberculosis and comorbidities: treatment challenges in patients with comorbid diabetes mellitus and depression[J]. Ther Adv Infect Dis, 2022, 9: 20499361221095831.
[30] ZHENG HX, HUANG Y, FRASSETTO LA, et al.Elucidating rifampin's inducing and inhibiting effects on glyburide pharmacokinetics and blood glucose in healthy volunteers: unmasking the differential effects of enzyme induction and transporter inhibition for a drug and its primary metabolite[J]. Clin Pharmacol Ther, 2009, 85(1): 78-85.
[31] KAJOSAARI LI, LAITILA J, NEUVONEN PJ, et al.Metabolism of repaglinide by CYP2C8 and CYP3A4 in vitro: effect of fibrates and rifampicin[J]. Basic Clin Pharmacol Toxicol, 2005, 97(4): 249-256.
[32] TORNIO A, NIEMI M, NEUVONEN PJ, et al.Drug interactions with oral antidiabetic agents: pharmacokinetic mechanisms and clinical implications[J]. Trends Pharmacol Sci, 2012, 33(6): 312-322.
[33] 国家感染性疾病临床医学研究中心, 深圳市第三人民医院, 国家代谢性疾病临床医学研究中心, 等. 结核病与糖尿病共病的治疗管理专家共识[J]. 中国防痨杂志, 2021, 43: 12-22.
[34] LONDHE O, SANJAY MANE S, UMESH HIRLEKAR B, et al.In vitro, in-vivo, and in-silico investigation of physicochemical interactions between pioglitazone and rifampicin[J]. Eur J Pharm Biopharm, 2023, 188: 54-65.
[35] BACKMAN JT, FILPPULA AM, NIEMI M, et al.Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions[J]. Pharmacol Rev, 2016, 68(1): 168-241.
[36] TRIVEDI P, CHATURVEDI V.Interactive effect of oral anti-hyperglycaemic or anti-hypertensive drugs on the inhibitory and bactericidal activity of first line anti-TB drugs against M. tuberculosis[J]. PLoS One, 2023, 18(11): e0292397.
[37] 马翠, 谢珊珊, 林环玉, 等. 系统综述新型口服抗凝药与抗菌药物相互作用[J]. 临床合理用药, 2023, 16: 174-177.
[38] 罗廷茹,孙楠楠. 利福平联合艾多沙班治疗肺结核合并深静脉血栓形成1例报道[J/CD].新发传染病电子杂志,2023,8(6):69-72.
[39] GOLDSTEIN R, JACOBS AR, ZIGHAN L, et al.Interactions Between Direct Oral Anticoagulants (DOACs) and Antiseizure Medications: Potential Implications on DOAC Treatment[J]. CNS Drugs, 2023, 37(3): 203-214.
[40] ROGERS KC, NEU DW, JAEGER MC, et al.An Underappreciated and Prolonged Drug Interaction Leads to Ineffective Anticoagulation[J]. South Med J, 2019, 112(2): 125-129.
[41] LUTZ JD, KIRBY BJ, WANG L, et al.Cytochrome P450 3A Induction Predicts P-glycoprotein Induction; Part 1: Establishing Induction Relationships Using Ascending Dose Rifampin[J]. Clin Pharmacol Ther, 2018, 104(6): 1182-1190.
[42] LUTZ JD, KIRBY BJ, WANG L, et al.Cytochrome P450 3A Induction Predicts P-glycoprotein Induction; Part 2: Prediction of Decreased Substrate Exposure After Rifabutin or Carbamazepine[J]. Clin Pharmacol Ther, 2018, 104(6): 1191-1198.
[43] MACDOUGALL C, CANONICA T, KEH C, et al.Systematic review of drug-drug interactions between rifamycins and anticoagulant and antiplatelet agents and considerations for management[J]. Pharmacotherapy, 2022, 42(4): 343-361.
[44] TODA A, UEHARA S, INOUE T, et al.Effects of aging and rifampicin pretreatment on the pharmacokinetics of human cytochrome P450 probes caffeine, warfarin, omeprazole, metoprolol and midazolam in common marmosets genotyped for cytochrome P450 2C19[J]. Xenobiotica, 2018, 48(7): 720-726.
[45] JUDGE HM, PATIL SB, BUCKLAND RJ, et al.Potentiation of clopidogrel active metabolite formation by rifampicin leads to greater P2Y12 receptor blockade and inhibition of platelet aggregation after clopidogrel[J]. J Thromb Haemost, 2010, 8(8): 1820-1827.
[46] FARID NA, JAKUBOWSKI JA, PAYNE CD, et al.Effect of rifampin on the pharmacokinetics and pharmacodynamics of prasugrel in healthy male subjects[J]. Curr Med Res Opin, 2009, 25(8): 1821-1829.
[47] CZYRSKI A, RESZTAK M, WIDERSKI P, et al.The Overview on the Pharmacokinetic and Pharmacodynamic Interactions of Triazoles[J]. Pharmaceutics, 2021, 13(11).
[48] SCHWIESOW JN, ISEMAN MD, PELOQUIN CA.Concomitant use of voriconazole and rifabutin in a patient with multiple infections[J]. Pharmacotherapy, 2008, 28(8): 1076-1080.
[49] KIM Y, BAE S, HUH KY, et al.Coadministration of Voriconazole and Rifabutin Can Increase the Risk of Adverse Drug Reactions in Patients with Multiple Infections[J]. Ther Drug Monit, 2024.
[50] BELLMANN R, SMUSZKIEWICZ P.Pharmacokinetics of antifungal drugs: practical implications for optimized treatment of patients[J]. Infection, 2017, 45(6): 737-779.
[51] NKUIZE M, DE WIT S.Issues Related to the Treatment of H. pylori Infection in People Living with HIV and Receiving Antiretrovirals[J]. Microorganisms, 2022, 10(8).
[52] KEMPKER RR, ALGHAMDI WA, AL-SHAER MH, et al.A Pharmacology Perspective of Simultaneous Tuberculosis and Hepatitis C Treatment[J]. Antimicrob Agents Chemother, 2019, 63(12).
[53] 马世武, 王嘉睿, 朱娅梅. 结核合并丙型肝炎病毒感染同时治疗的药物选择[J]. 中华肝脏病杂志, 2022, 30(1): 4.
[54] ASHKIN A, ALEXIS A, NINNEMAN M, et al. Concomitant Treatment of Tuberculosis and Hepatitis C Virus in Coinfected Patients Using Serum Drug Concentration Monitoring[J]. Open Forum Infect Dis, 2023, 10(6): ofad237.
[55] SUN L, MCDONNELL D, YU M, et al.A Phase I Open-Label Study to Evaluate the Effects of Rifampin on the Pharmacokinetics of Olanzapine and Samidorphan Administered in Combination in Healthy Human Subjects[J]. Clin Drug Investig, 2019, 39(5): 477-484.
[56] 陈文忠, 谢帆, 顾文明, 等. 利福喷丁与利福布汀对氯氮平血药浓度和疗效的影响[J]. 中国防痨杂志, 2015, 37: 943-947.
[57] 金弢. 含利福平方案治疗结核病时需用免疫抑制剂的剂量调整(附3例报告)[J]. 中国防痨杂志, 2018, 40(9): 5.
[58] 中华医学会血液学分会, 中华医学会结核病学分会. 异基因造血干细胞移植患者合并结核分枝杆菌感染诊断与治疗中国专家共识(2023年版)[J]. 中华血液学杂志, 2023, 44(2): 98-105.
[59] WANG YC, SALVADOR NG, LIN CC, et al.Comparative analysis of the drug-drug interaction between immunosuppressants, safety and efficacy of rifabutin from rifampicin-based Anti-TB treatment in living donor liver transplant recipients with active tuberculosis[J]. Biomed J, 2021, 44(6 Suppl 2): S162-S170.
[60] ASIF M, QUSTY NF, ALGHAMDI S.An Overview of Various Rifampicin Analogs against Mycobacterium tuberculosis and their Drug Interactions[J]. Med Chem, 2024, 20(3): 268-292.
[61] PHILLIPS MC, WALD-DICKLER N, LOOMIS K, et al. Pharmacology, Dosing,Side Effects of Rifabutin as a Possible Therapy for Antibiotic-Resistant Acinetobacter Infections[J]. Open Forum Infect Dis, 2020, 7(11): ofaa460.
[62] MARMOR M, SHARIFI H, JACOBS S, et al.Variables associated with antibiotic treatment tolerance in patients with Mycobacterium avium complex pulmonary disease[J]. Respir Res, 2024, 25(1): 123.
[63] WANG Z, BEUGNIES E, RACHDI M, et al.Rifabutin-induced uveitis: A jellyfish in the eye[J]. J Fr Ophtalmol, 2024, 47(8): 104266.
[64] SAHYOUN JY, SABETI S, ROBERT MC.Drug-induced corneal deposits: an up-to-date review[J]. BMJ Open Ophthalmol, 2022, 7(1): e000943.