Pharmacology
Mechanism of action
Rifampicin inhibits bacterial DNA-dependent RNA synthesis by inhibiting bacterial DNA-dependent RNA polymerase.Crystal structure data and biochemical data suggest that rifampicin binds to the pocket of the RNA polymerase β subunit within the DNA/RNA channel, but away from the active site. The inhibitor prevents RNA synthesis by physically blocking elongation, and thus preventing synthesis of host bacterial proteins. By this "steric-occlusion" mechanism, rifampicin blocks synthesis of the second or third phosphodiester bond between the nucleotides in the RNA backbone, preventing elongation of the 5 end of the RNA transcript past more than 2 or 3 nucleotides.In a recent study Rifampicin was shown to bind to cytochrome P450 reductase and alter its conformation as well as activity towards supporting metabolism of progesterone via CYP21A2. Mechanism of resistance
Resistance to rifampicin arises from mutations that alter residues of the rifampicin binding site on RNA polymerase, resulting in decreased affinity for rifampicin. Resistance mutations map to the rpoB gene, encoding the beta subunit of RNA polymerase. The majority of resistance mutations in E. coli are in 3 clusters on rpoB. Cluster I is amino acids 509 to 533, cluster II is amino acids 563 to 572, and cluster III is amino acid 687. When describing mutations in rpoB in other species, the corresponding amino acid number in E. coli is usually used. In Mycobacterium tuberculosis, the majority of mutations leading to rifampicin resistance are in cluster I, in a 81bp hotspot core region called RRDR for "rifampcin resistance determining region".
MNP belongs to the nitrosamine class of compounds, some of which are classified as probable or possible human carcinogens (substances that could cause cancer), based on laboratory tests such as rodent carcinogenicity studies. Although there are no data available to directly evaluate the carcinogenic potential of MNP, information available on closely related nitrosamine compounds was used to calculate lifetime exposure limits for MNP.As of January 2021, the FDA continues to investigate the presence of 1-methyl-4-nitrosopiperazine (MNP) in rifampin or 1-cyclopentyl-4-nitrosopiperazine (CPNP) in rifapentine approved for sale in the US. Names
Rifampicin is the INN and BAN, while rifampin is the USAN. Rifampicin may be abbreviated R, RMP, RA, RF, or RIF (US). Rifampicin is also known as rifaldazine, rofact, and rifampin in the United States, also as rifamycin SV.Its chemical name is 5,6,9,17,19,21-hexahydroxy-23-methoxy-2,4,12,16,18,20,22-heptamethyl-8-[N-(4-methyl-1-piperazinyl)formimidoyl]-2,7-(epoxypentadeca[1,11,13]trienimino)-naphtho[2,1-b]furan-1,11(2H)-dione 21-acetate. Rifampicin is available under many brand names worldwide. References
External links
"Rifampicin". Drug Information Portal. U.S. National Library of Medicine.