Rifampicin Impurities

Rifampin, also known as rifampicin, is a broad-spectrum antimicrobial 1 that was first discovered in 1965 2 and clinically used in 1968. 6. It is an ansamycin class antibiotic that exerts bactericidal activity by binding to the beta subunit of the bacterial DNA-dependent RNA polymerase rpoB and blocking transcription initiation; this mechanism confers potent activity against Mycobacterium tuberculosis and other mycobacteria and against many Gram positive organisms and selected Gram negative pathogens when used in combination therapy. Chemically it contains a substituted naphthohydroquinone chromophore linked to an aliphatic ansa chain; the drug is lipophilic with limited aqueous solubility, extensively protein bound, and undergoes hepatic deacetylation to an active metabolite desacetylrifampicin. Rifampin is orally active with variable bioavailability and shows enzyme induction of hepatic cytochromes particularly CYP3A4, which accelerates metabolism of many concomitant drugs and of rifampin itself on repeated dosing through autoinduction, producing a shorter terminal half life during chronic therapy. Clinical use is primarily in combination regimens for tuberculosis, as part of multidrug therapy for certain mycobacterial infections, and for chemoprophylaxis of meningococcal carriage; dosing considerations include drug interactions, hepatic function monitoring, and awareness of characteristic orange discoloration of body fluids.