Abstract

RIFAMPICIN: A COMPREHENSIVE REVIEW OF ITS MECHANISM, THERAPEUTIC APPLICATIONS, PHARMACOLOGY, RESISTANCE PATTERNS, AND FUTURE PERSPECTIVES

Anant Mangrulkar*, Mrs. Seema Rathod, Dr. Sunil Jaybhaye

ABSTRACT

Rifampicin is a cornerstone antimicrobial agent primarily used in the treatment of tuberculosis (TB) and other mycobacterial infections. Discovered in the 1960s, this semisynthetic derivative of rifamycin has played a pivotal role in combating infectious diseases globally. Rifampicin exerts its antimicrobial effect by inhibiting bacterial DNA-dependent RNA polymerase, thereby suppressing transcription and subsequent protein synthesis. This unique mechanism of action underlies its potent activity against a broad spectrum of Gram-positive and some Gram-negative bacteria, as well as its bactericidal efficacy against Mycobacterium tuberculosis. The pharmacokinetics of rifampicin reveal its high oral bioavailability, extensive tissue distribution, and primary hepatic metabolism via the cytochrome P450 system, particularly CYP3A4. It undergoes enterohepatic recirculation, with elimination primarily through bile and feces. The pharmacodynamic profile is characterized by a concentration-dependent killing effect and a post-antibiotic effect against susceptible organisms. Therapeutic uses of rifampicin extend beyond TB to include the management of leprosy, brucellosis, and prosthetic joint infections, as well as prophylaxis for meningococcal and Haemophilus influenzae type b infections. Safety and tolerability of rifampicin are generally favorable, though its long-term use is associated with adverse effects such as hepatotoxicity, gastrointestinal disturbances, and flu-like symptoms. Rifampicin is also a potent inducer of cytochrome P450 enzymes, leading to significant drug-drug interactions that can complicate its use in patients with comorbid conditions requiring polypharmacy. Additionally, rifampicin resistance, primarily arising from mutations in the rpoB gene encoding the RNA polymerase β-subunit, poses a significant rifampicin reveal its high oral bioavailability, extensive tissue distribution, and primary hepatic metabolism via the cytochrome P450 system, particularly CYP3A4. It undergoes enterohepatic recirculation, with elimination primarily through bile and feces. The pharmacodynamic profile is characterized by a concentration-dependent killing effect and a post-antibiotic effect against susceptible organisms. Therapeutic uses of rifampicin extend beyond TB to include the management of leprosy, brucellosis, and prosthetic joint infections, as well as prophylaxis for meningococcal and Haemophilus influenzae type b infections. Safety and tolerability of rifampicin are generally favorable, though its long-term use is associated with adverse effects such as hepatotoxicity, gastrointestinal disturbances, and flu-like symptoms. Rifampicin is also a potent inducer of cytochrome P450 enzymes, leading to significant drug-drug interactions that can complicate its use in patients with comorbid conditions requiring polypharmacy. Additionally, rifampicin resistance, primarily arising from mutations in the rpoB gene encoding the RNA polymerase β-subunit, poses a significant 

Keywords: Antibiotic resistance, Tuberculosis treatment, Multidrug-resistant tuberculosis (MDR-TB), Efflux pumps, Hepatotoxicity, Combination therapy, Rifamycin derivatives, Antimicrobial stewardship, Drug resistance mechanisms, Therapeutic efficacy, Molecular diag