Rifampicin
[CAS# 13292-46-1]

Identification

• Classification: API >> Antibiotics >> Rifamycin
• Name: Rifampicin
• Synonyms: 3-[[(4-methyl-1-piperazinyl)imino]methyl]-rifamycin
• Molecular Formula: C₄₃H₅₈N₄O₁₂
• Molecular Weight: 822.95
• CAS Registry Number: 13292-46-1
• EC Number: 236-312-0
• SMILES: C[C@H]1/C=C/C=C(C(=O)NC2=C(C(=C3C(=C2O)C(=C(C4=C3C(=O)[C@](O4)(O/C=C/[C@@H]([C@H]([C@H]([C@@H]([C@@H]([C@@H]([C@H]1O)C)O)C)OC(=O)C)C)OC)C)C)O)O)/C=N/N5CCN(CC5)C)/C

Properties

• Solubility: 25 mg/mL (methanol), 25 mg/mL (DMSO) (Expl.)
• Density: 1.3±0.1 g/cm³, Calc.^*
• Melting Point: 194 °C (Expl.)
• Index of Refraction: 1.613, Calc.^*
• Boiling Point: 1004.4±65.0 °C (760 mmHg), Calc.^*
• Flash Point: 561.3±34.3 °C, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H319-H335
• Safety Statements: P261-P264-P264+P265-P270-P271-P280-P301+P317-P302+P352-P304+P340-P305+P351+P338-P319-P321-P330-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319
Specific target organ toxicity - single exposure	STOT SE	3	H335
Acute toxicity	Acute Tox.	4	H312
Reproductive toxicity	Repr.	2	H361
Acute toxicity	Acute Tox.	4	H332
Reproductive toxicity	Lact.	-	H362
Reproductive toxicity	Repr.	1A	H360
Carcinogenicity	Carc.	2	H351
Reproductive toxicity	Repr.	1B	H360
Chronic hazardous to the aquatic environment	Aquatic Chronic	2	H411
Acute toxicity	Acute Tox.	2	H300
Acute toxicity	Acute Tox.	2	H310
Specific target organ toxicity - single exposure	STOT SE	3	H336
Acute toxicity	Acute Tox.	2	H330

Discovery and Applications

Rifampicin is a widely known antibiotic that is primarily used in the treatment of bacterial infections, particularly tuberculosis (TB). It was first discovered in the 1950s by researchers at the Swiss pharmaceutical company Hoffmann-La Roche, who isolated it from the bacterium *Streptomyces mediterranei*. Rifampicin is a member of the rifamycin class of antibiotics, which are characterized by their ability to inhibit bacterial RNA synthesis.

Rifampicin works by binding to the bacterial RNA polymerase enzyme, specifically to the beta-subunit of the enzyme. This binding inhibits the enzyme's ability to initiate transcription, effectively preventing the bacteria from synthesizing RNA and, therefore, proteins. This action makes rifampicin a bactericidal agent, killing susceptible bacteria rather than merely inhibiting their growth.

One of the most important applications of rifampicin is in the treatment of tuberculosis, especially when combined with other antituberculosis drugs in multi-drug regimens. Rifampicin is considered a cornerstone in the management of TB due to its ability to penetrate bacterial cells and reach high concentrations in tissues affected by the infection. Its use in combination therapy helps prevent the development of drug resistance, which is a major concern in the treatment of TB.

In addition to its use in tuberculosis, rifampicin is also employed in the treatment of other bacterial infections, such as leprosy and certain types of staphylococcal infections. It is sometimes used as a prophylactic treatment for meningococcal infections, particularly in individuals who have been in close contact with someone who has the disease.

Rifampicin is typically administered orally in the form of capsules or tablets, but it can also be given intravenously for more serious infections. The drug is well-absorbed in the gastrointestinal tract, and it is metabolized in the liver. Due to its potent effects and the potential for side effects, the use of rifampicin is carefully monitored. Common side effects include liver toxicity, gastrointestinal disturbances, and changes in urine color (a harmless but characteristic red-orange discoloration).

Resistance to rifampicin can occur through mutations in the bacterial RNA polymerase gene, and such resistance is of particular concern in the context of tuberculosis treatment. This underscores the importance of using rifampicin in combination with other drugs as part of a comprehensive treatment regimen to reduce the likelihood of resistance.

Rifampicin has also been studied for its ability to influence the metabolism of other drugs, as it is a potent inducer of cytochrome P450 enzymes in the liver. This can lead to interactions with other medications, affecting their metabolism and potentially reducing their efficacy.

In summary, rifampicin is an essential antibiotic with a significant role in treating tuberculosis and other bacterial infections. Its discovery and development have had a profound impact on the management of bacterial diseases, particularly those caused by drug-resistant organisms. Its broad-spectrum antibacterial activity and critical role in combination therapy continue to make it a key tool in modern medicine.

References

2021. A multi-centre, open label, randomised, parallel-group, superiority Trial to compare the efficacy of URsodeoxycholic acid with RIFampicin in the management of women with severe early onset Intrahepatic Cholestasis of pregnancy: the TURRIFIC randomised trial. BMC Pregnancy and Childbirth, 21(1).
DOI: 10.1186/s12884-020-03481-y

2021. Discovery of a highly potent novel rifampicin analog by preparing a hybrid of the precursors of the antibiotic drugs rifampicin and clofazimine. Scientific Reports, 11(1).
DOI: 10.1038/s41598-020-80439-2

1971. Assembly of virus particles during mixed infection with wild-type vaccinia and a rifampicin-resistant mutant. Virology, 45(1).
DOI: 10.1016/0042-6822(71)90120-6