RNA polymerase
Rifampin (Rifampicin) targets bacterial RNA polymerase β subunit (rpoB) (Ki=0.02 μM for Mycobacterium tuberculosis RNA polymerase; IC50=0.05 μM for Staphylococcus aureus RNA polymerase)[3]
Rifampin (Rifampicin) specifically inhibits Mycobacterium leprae RNA polymerase (EC50=0.03 μM)[2]

Rifampin prevents the phosphorylation of mitogen-activated protein kinase (MAPK) and the degradation of IκBα. It is discovered that the binding between rifampin and human MD-2 is concentration-dependent. NF-κB activation triggered by LPS (20 ng/ml) is inhibited by rifampin in a dose-dependent manner, with an IC50 of 44.1 μM in immunocompetent microgial BV-2 cell and Blue hTLR4 293 cells (A). The maximum NF-κB level induced by LPS in the presence of Rifampin (50 μM) is significantly lower than that in the absence of Rifampin. Rifampin (50 μM) suppresses NF-κB activation at varying LPS doses. Rifampin, with an IC50 of 21.2 μM, inhibits NO production in BV-2 cells in a dose-dependent manner when LPS (200 ng/ml) is added. In both microglia BV-2 and RAW 264.7 macrophage cells, rifampin inhibits the production of TNF-α and IL-1β induced by LPS. The pregnane X receptor (NR1I2) is not necessary for rifampin-inhibiting innate immune signaling.[1] When rifampin is combined with polyester vascular prostheses (PVP) functionalized with cyclodextrin (PVP-CD), it significantly reduces bacterial adhesion and inhibits Gram-positive bacteria's ability to grow.[2] In stationary-phase cultures, Rifampin (50 μg/mL) significantly lowers the CFU counts, and in log-phase cultures, it completely eliminates the CFU counts. Since rifampin is bactericidal and begins to kill M. tuberculosis within an hour of exposure, it is especially appropriate.[3]

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Anti-Mycobacterium tuberculosis activity: Minimum inhibitory concentration (MIC) against M. tuberculosis H37Rv was 0.06 μg/mL; MIC range against isoniazid- and streptomycin-resistant clinical isolates was 0.06~0.25 μg/mL, maintaining potent inhibition[3]
- Anti-gram-positive bacterial activity: MIC50=0.1 μg/mL and MIC90=0.2 μg/mL for Staphylococcus aureus (including MRSA); MIC range for coagulase-negative staphylococci was 0.05~0.1 μg/mL[2]
- Anti-Mycobacterium leprae activity: 0.03 μM Rifampin inhibited 50% bacterial growth in primary M. leprae cultures, with an inhibition rate of 99% at 0.5 μM[2]
- Mechanism verification: Binding to the β subunit of bacterial RNA polymerase blocks the formation of the transcription initiation complex and inhibits RNA synthesis; in in vitro transcription assays, 0.1 μM drug reduced M. tuberculosis RNA synthesis by 90%[3]
- Resistance-related experiments: After rpoB codon 531 mutation (Ser→Leu), the MIC of M. tuberculosis to the drug increased to 8 μg/mL, with a resistance fold of 133[3]
- Low cytotoxicity: CC50 values were >100 μg/mL in primary human alveolar epithelial cells and macrophages, with a therapeutic index (CC50/MIC) >1600[1]

Rifampicin (200, 400 mg/kg) can cause fatty liver at high concentration. In vivo treatment of S464P biofilms with rifampicin (30 mg/kg, i.p.) causes a slight decrease, but earlier rebinds in bioluminescence from these catheters in comparison to the parental signal; in contrast, rifampicin has no effect on bioluminescence in mice infected with mutant H481Y.

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Mouse M. tuberculosis infection model (H37Rv intravenous inoculation): Oral administration of Rifampin 10 mg/kg once daily for 28 days reduced lung M. tuberculosis colony-forming units (CFU) from 10⁶ to 10² CFU/g, liver CFU to 10¹ CFU/g, and reduced pulmonary inflammatory lesion area by 80%[1]
- Rat M. leprae infection model: Oral Rifampin 15 mg/kg once weekly for 12 weeks reduced skin M. leprae load by 5 log10 CFU/g, with a skin ulcer healing rate of 75%[2]
- Mouse S. aureus sepsis model: Intraperitoneal injection of Rifampin 20 mg/kg every 12 hours for 5 days achieved a 98% bacterial clearance rate in blood and increased mouse survival rate from 30% to 85%[2]
- Synergistic effect of combination therapy: Combined oral administration with isoniazid (10 mg/kg) for mouse tuberculosis reduced lung CFU by an additional 1 log10 compared with monotherapy, shortening the treatment cycle from 28 days to 21 days[1]

Bacterial RNA polymerase activity inhibition assay: Recombinant RNA polymerase (α2ββ'σ subunit complex) purified from M. tuberculosis was incubated with serial concentrations of Rifampin (0.001~1 μM) in a reaction system containing DNA template and NTP substrates for 30 minutes. After incubation at 37°C for 1 hour, RNA synthesis products were detected by autoradiography. Results showed 50% enzyme activity inhibition at 0.02 μM (Ki=0.02 μM) with concentration-dependent competitive inhibition[3]
- Drug-resistant mutant enzyme binding assay: rpoB Ser531Leu mutant RNA polymerase was constructed and incubated with Rifampin, and binding affinity was detected by isothermal titration calorimetry (ITC). The binding constant (KD) of the mutant enzyme to the drug was 300-fold higher than that of the wild-type, confirming loss of drug binding ability due to mutation[3]
- Gram-positive bacterial RNA polymerase inhibition assay: Purified S. aureus RNA polymerase was added with different drug concentrations, and transcription activity was detected using a luciferase reporter system. 0.05 μM Rifampin inhibited 50% transcription activity (IC50=0.05 μM)[3]

Bacterial MIC determination (broth dilution method): M. tuberculosis and S. aureus were inoculated into media containing serial concentrations of Rifampin (0.01~16 μg/mL) and cultured at 37°C for 72 hours (14 days for M. tuberculosis). Bacterial growth was observed, and the minimum drug concentration inhibiting 50% (MIC50) and 90% (MIC90) bacterial growth was recorded[2]
- Bacterial transcription inhibition assay: M. tuberculosis H37Rv was inoculated into media containing 0.06~0.5 μg/mL Rifampin, and after 24 hours of culture, total bacterial RNA was extracted. 16S rRNA synthesis was detected by real-time quantitative PCR. The RNA synthesis in the 0.1 μg/mL drug treatment group decreased by 85% compared with the control group[3]
- Cytotoxicity assay (CCK-8 method): Primary human alveolar epithelial cells were seeded in 96-well plates at 1×10⁴ cells/well, incubated for 24 hours, and then treated with 0.1~200 μg/mL Rifampin for 72 hours. CCK-8 reagent was added for incubation for 2 hours, and absorbance at 450 nm was measured to calculate CC50 values[1]
- Drug-resistant strain screening assay: M. tuberculosis H37Rv was serially passaged 30 times in media containing subinhibitory concentration (0.03 μg/mL) of Rifampin. rpoB gene mutations were detected by sequencing, and the MIC of the passaged strains was determined[3]

In brief, groups of nine mice per strain receive subcutaneous implants of a 1 cm Teflon (14-gauge) catheter containing 104 cfu S. aureus, either the parental strain Xen 29 or the RifR mutants S464P or H481Y. Every animal has one catheter segment inserted on each side. Five mice per group are given rifampicin (30 mg/kg) intraperitoneally in 0.1 mL saline twice a day for four days straight, six days after the catheters are implanted. As controls, each group's final four mice are not given any medication. The IVIS ® manifold is used to continuously flow 1.5% isoflurane to anesthetize the mice at different stages of the infection. An IVIS ® Image System 100 Series is then used to image the mice. During the course of the infection, the bioluminescent signals (photons/s) that the mice emit are plotted and analyzed using LivingImage ® software. Eleven days after the last rifampicin treatment, or twenty days after infection, the mice are killed. To assess the amount of bacteria on the catheters, the catheters are surgically removed, and the bacteria are separated using sonication.

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Mouse M. tuberculosis infection model: C57BL/6 mice were intravenously inoculated with M. tuberculosis H37Rv (10⁵ CFU/mouse), and drug administration started on day 7 post-infection. Rifampin was dissolved in 0.5% carboxymethylcellulose sodium solution to prepare a 1 mg/mL suspension, administered orally at 10 mg/kg once daily for 28 days. Some mice were sacrificed every 7 days, lung and liver tissues were isolated, homogenized, and inoculated into media to count CFU. Meanwhile, lung tissue pathological sections were analyzed[1]
- Rat M. leprae infection model: Wistar rats were intradermally inoculated with M. leprae (10⁶ CFU/rat), and drug administration started on day 30 post-infection. The drug was dissolved in normal saline, administered orally at 15 mg/kg once weekly for 12 weeks. Skin tissue samples were collected every 4 weeks to detect bacterial load and observe skin ulcer healing[2]
- Mouse S. aureus sepsis model: BALB/c mice were intraperitoneally inoculated with S. aureus (10⁷ CFU/mouse), and drug administration started 2 hours post-infection. Rifampin was dissolved in normal saline, administered intraperitoneally at 20 mg/kg every 12 hours for 5 days. Mouse survival status was observed daily, and blood samples were collected on day 5 to count bacterial load by plating media[2]
- Combination therapy model: After M. tuberculosis infection in C57BL/6 mice, Rifampin (10 mg/kg, oral, once daily) was combined with isoniazid (10 mg/kg, oral, once daily) for 21 consecutive days. Lung and liver tissue CFU and inflammatory indicators were detected[1]

Absorption, Distribution and Excretion
Absorbed well via the gastrointestinal tract. Less than 30% of the dose is excreted in the urine as rifampin or its metabolites. 0.19 +/- 0.06 L/hr/kg [300 mg IV] 0.14 +/- 0.03 L/hr/kg [600 mg IV] Rifampin is distributed throughout the body, reaching effective concentrations in many organs and body fluids, including cerebrospinal fluid. The drug may give urine, feces, saliva, sputum, tears, and sweat an orange-red hue, perhaps best illustrating this… Up to 30% of the drug dose is excreted in the urine and 60% to 65% in the feces; less than half of this may be the unchanged antibiotic. Peak plasma concentrations are reached within 2 to 4 hours after oral administration of rifampin; after a 600 mg dose, the plasma concentration is approximately 7 μg/mL, but there is considerable individual variability.
Rifampin is absorbed from the gastrointestinal tract and rapidly excreted via bile, entering the enterohepatic circulation.
For more complete data on the absorption, distribution, and excretion of rifampin (10 items), please visit the HSDB records page.

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Metabolism/Metabolites
Primarily metabolized in the liver, rapidly deacetylated.
The effects of rifampin…and phenobarbital…on the metabolism of isoniazid…and hydrazine… were investigated in rats. Male Wistar rats were fasted and then pretreated with intraperitoneal injections of rifampin (30 mg/kg for 6 days) or phenobarbital (50 mg/kg for 3 days). After pretreatment, rats were intraperitoneally injected with isoniazid (40 mg/kg). 24-hour urine samples were collected, and the concentrations of hydrazine and acetylhydrazine in the urine were determined by gas chromatography/mass spectrometry. After sacrifice, rats were immediately perfused and homogenized in situ, and the distribution of metabolites in the liver was determined. Blood samples were collected, and plasma hydrazine concentrations were measured at 0.5, 1, 2, 3, and 4 hours after intravenous injection of 5 mg/kg hydrazine. Hydrazine and acetylhydrazine were detectable in the liver and plasma within 1 hour after isoniazid injection. Hydrazine concentrations in the rifampicin or phenobarbital pretreatment groups were significantly lower than in the control group; acetylhydrazine concentrations remained unchanged. Rifampicin or phenobarbital pretreatment significantly increased urinary hydrazine excretion. ...
In guinea pigs, rabbits, and humans, the major metabolite of rifampicin in urine and bile is 25-O-deacetylated rifampicin; an unidentified metabolite was detected in the body fluids of dogs and mice.
Rifampicin is metabolized in the liver to a deacetylated derivative, which also possesses antibacterial activity.
Several rapidly growing mycobacterial strains have been found to inactivate rifampicin. The two inactivating compounds (RIP-Ma and RIP-Mb) produced by these microorganisms differ from previously reported antibiotic derivatives (i.e., phosphorylated or glycosylated derivatives). The structures of RIP-Ma and RIP-Mb were determined to be 3-formyl-23-[O-(α-D-rifuranosyl)]rifamycin SV and 23-[O-(α-D-rifuranosyl)]rifapine, respectively. To our knowledge, this is the first report of ribosylation as an antibiotic inactivation mechanism.
Biological half-life
3.35 (± 0.66) hours
The half-life of rifampin is 1.5 to 5 hours, and is prolonged in patients with hepatic impairment; in patients taking isoniazid concurrently, the half-life may be shortened due to the slow inactivation of rifampin.Due to the induction of hepatic microsomal enzymes, drug deacetylation is accelerated, and the half-life of rifampin gradually shortens by about 40% in the first 14 days of treatment.
In children aged 6–58 months, the mean plasma half-life after a single oral dose of 10 mg/kg rifampin is 2.9 hours. In children aged 3 months to 12.8 years, the plasma half-life of rifampin administered intravenously was 1.04-3.81 hours in the first few days of treatment, and decreased to 1.17-3.19 hours after 5-14 days of treatment.

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Absorption: The oral bioavailability in rats was 90%~95%; after a single oral dose of 10 mg/kg, the peak plasma concentration (Cmax) was 8 μg/mL, and the time to peak concentration (Tmax) was 2 hours[1]
-Distribution: High drug concentrations were found in lung, liver, spleen and kidney tissues; after oral administration of 10 mg/kg to rats, the drug concentration in lung tissue was 3.2 times that in plasma; the concentration in cerebrospinal fluid was 10%~20% of the plasma concentration, and could increase to 30% in inflammatory states[1]
-Metabolism: It is mainly metabolized in the liver by cytochrome P450 3A4 enzyme, and the main metabolite is deacetylated rifampin, which still has antibacterial activity (MIC is 2~4 times that of the original drug)[1]
- Excretion: Within 72 hours after administration to rats, fecal excretion accounted for 60% to 70% of the administered dose (mainly metabolites), and urinary excretion accounted for 15% to 20% (5% of the original drug) [1] - Half-life: The elimination half-life (t1/2) after oral administration to rats was 3.5 to 4.5 hours; the half-life after intravenous injection was 3 to 3.5 hours [1] - Plasma protein binding rate: In vitro experiments showed that the plasma protein binding rate of this drug in human plasma was 85% to 90%, mainly bound to albumin [1]

Toxicity Summary
Identification: Rifampin is an antibiotic used to treat tuberculosis. Rifampin is a semi-synthetic derivative of rifamycin antibiotics, which are produced by fermentation of Streptomyces mediterranei. This fermentation process produces rifamycin B. Rifamycin B is derived through a series of synthetic reactions. Color: Red to orange odorless powder. Slightly soluble in water, acetone, carbon tetrachloride, ethanol, and ether. Frequently soluble in chloroform and dimethyl sulfoxide (DMSO); soluble in ethyl acetate, methanol, and tetrahydrofuran. Its solubility in aqueous solution increases under acidic pH conditions. Melting point: 138 to 188 °C. Rifampin has two pKa values because it is an amphoteric ion: pKa 1.7 is associated with 4-hydroxyl, and pKa 7.9 is associated with 3-piperazine nitrogen. A 1% rifampin aqueous suspension has a pH of 4.5 to 6.5. Indications: The primary indications for rifampin are the treatment of tuberculosis (pulmonary and extrapulmonary tuberculosis) and leprosy. It can also be used to clear Neisseria meningitidis from carriers (but is not recommended for active meningococcal infections), as well as Gram-positive bacteria (Staphylococcus aureus and Staphylococcus epidermidis, Streptococcus pyogenes, Streptococcus viridans, and Streptococcus pneumoniae) and Gram-negative bacteria (Haemophilus influenzae type B). Rifampin has some anti-chlamydial activity and, at high doses, in vitro activity against certain viruses (poxviruses and adenoviruses). In recent years, rifampin has also been used to treat brucellosis. Human Exposure: Main Risks and Target Organs: The main target organs are the liver and gastrointestinal system. Risks of concern include toxic hepatitis (with elevated bile and bilirubin levels), anemia, leukopenia, thrombocytopenia, and bleeding. Clinical Effects Overview: Some clinical manifestations of overdose are exacerbations of adverse reactions. Rifampin is generally well tolerated during treatment, but adverse reactions are common with intermittent use. These adverse reactions include fever, eosinophilia, leukopenia, thrombocytopenia, purpura, hemolysis and shock, hepatotoxicity, and nephrotoxicity. Gastrointestinal adverse reactions can be severe, even leading to pseudomembranous colitis. Neurotoxic effects include confusion, ataxia, blurred vision, dizziness, and peripheral neuritis. Common toxic reactions include skin redness and orange body fluids. There have been reports of death due to adverse reactions. Rifampin has no significant effect on human fetuses. Rifampin can diffuse into breast milk and other body fluids. Contraindications: Rifampin is contraindicated in patients with known hypersensitivity to it. It is contraindicated during pregnancy (because animal studies have shown its teratogenicity, and the effects of the drug on the fetus have not been determined), unless the patient has a serious condition such as tuberculosis. It is contraindicated in patients with severe hepatic impairment, alcoholism, and jaundice. Route of administration: Oral: This is the most common route of administration. Ophthalmic: Used to treat ocular chlamydia infections. Administration by injection: Rifampin can be administered intravenously. Pharmacokinetics: Absorption: Rifampin is readily absorbed from the gastrointestinal tract (90%). Peak plasma concentrations are reached 1.5 to 4 hours after oral administration. Food may reduce and delay absorption. Distribution by route of administration: Intravenous rifampin has the same distribution as oral administration. 89% of circulating rifampin is bound to plasma proteins. Rifampin is lipid-soluble and widely distributed throughout the body tissues and fluids. In cases of meningitis, rifampin can enter the cerebrospinal fluid. Therapeutic concentrations are typically achieved in lung and bronchial secretions, pleural effusions, other body cavity fluids, liver, bile, and urine. Rifampin has a high placental translocation rate, with a fetal-to-maternal serum concentration ratio of 0.3. Rifampin is distributed in breast milk. Apparent volume of distribution (VD) is 0.93–1.6 L/kg. Biological half-life determined by route of administration: The biological half-life is 3 hours (2–5 hours). High single-dose administration or liver disease can prolong the biological half-life. Due to increased bile excretion and auto-metabolic induction, the half-life of rifampin is shortened by 40% during the first two weeks of treatment. With repeated dosing, the plasma half-life may be further shortened. The half-life of rifampin is shortened from 3.5 hours at the start of treatment to 2 hours after 1 to 2 weeks of daily administration, and then remains stable. In anemia, the plasma half-life is shortened to 1.8 to 3.1 hours. Metabolism: Approximately 85% of rifampin is metabolized by hepatic microsomal enzymes to its main active metabolite, desacetylrifampin. Rifampin can undergo enterohepatic circulation, but desacetylrifampin cannot. Rifampin can increase its own metabolic rate. Rifampin may also be inactivated at other sites in the body. Formicylrifampin is a urinary metabolite and is spontaneously excreted in the urine. Clearance pathway: The rifampin metabolite desacetylrifampin is primarily excreted via bile and urine. Approximately 50% of the rifampicin dose is eliminated within 24 hours, with 6% to 30% excreted unchanged in the urine and 15% excreted as active metabolites. Approximately 43% to 60% of the oral dose is excreted in the feces. The intrinsic total clearance is 3.5 (± 1.6) mL/min/kg, decreasing in renal failure. Renal clearance is 8.7 mL/min/kg. Hemodialysis or peritoneal dialysis has no significant effect on plasma rifampicin concentrations. Rifampicin is excreted into breast milk (1 to 3 μg/ml). Mechanism of action: Toxicology: Rifampicin causes cholestasis of the hepatic sinusoids and hepatic tubules by inhibiting hepatocyte uptake and excretion, respectively. Rifampicin may cause hepatic dysfunction. The incidence of hepatitis is less than 1%, usually occurring in patients with a history of liver disease. Hypersensitivity reactions may occur, typically presenting as "flu-like" symptoms. Nephrotoxicity appears to be associated with hypersensitivity reactions, usually occurring intermittently or after discontinuation of treatment. Studies have shown that some adverse reactions of rifampin may be related to its metabolite, desacetylrifampin. Desacetylrifampin is lipid-soluble, thus it can reach and kill intracellular and extracellular mycobacteria. Rifampin does not bind to mammalian nuclear RNA polymerase, therefore it does not affect human RNA synthesis. However, the concentration of rifampin that affects mammalian mitochondrial RNA synthesis is 100 times higher than the concentration that affects bacterial RNA synthesis. Pharmacodynamics: Rifampin has high activity against mycobacteria, including Mycobacterium tuberculosis and Mycobacterium leprae. It is also effective against Staphylococcus aureus, coagulase-negative staphylococci, Listeria monocytogenes, Neisseria meningitidis, Haemophilus influenzae, Legionella spp., Brucella, certain strains of Escherichia coli, Proteus mirabilis, anaerobic cocci, Clostridium spp., and Bacteroides spp. Rifampin has also been reported to have immunosuppressive effects, which have been observed in some animal studies, but this effect may not be clinically significant in humans. The bacteriostatic or bactericidal effect of rifampin depends on the drug concentration at the site of infection. Its bactericidal effect is achieved by inhibiting the B subunit of bacterial DNA-dependent RNA polymerase, interfering with nucleic acid synthesis, and thus preventing the initiation of RNA transcription, but not affecting chain elongation. Carcinogenicity: One report showed that patients receiving rifampin treatment for two years may develop nasopharyngeal lymphoma. This may be due to the immunosuppressive effect of rifampin. Another report indicated that in a mouse strain, female mice treated with rifampin at 2% to 10% of the maximum human dose for one year had an increased incidence of liver cancer. Due to limited evidence regarding the carcinogenicity of rifampin in mice and the lack of epidemiological studies, the carcinogenicity of rifampin in humans cannot be assessed. Teratogenicity: There have been reports of birth defects and deaths in infants born to mothers who took rifampin, but the incidence was the same as in the general population. Drug Interactions: Food can interfere with the absorption of rifampin, thereby reducing peak plasma concentrations. Antacids containing aluminum hydroxide can reduce the bioavailability of rifampin. Para-aminosalicylic acid granules may delay the absorption of rifampin (because the granules contain bentonite as an excipient), leading to insufficient serum rifampin concentrations. These two medications should be taken 8 to 12 hours apart. The interaction between isoniazid and rifampin can cause hepatotoxicity. (Note: Slow acetylation of isoniazid accelerates the clearance of rifampin). Drinking alcohol while taking rifampin increases the risk of hepatotoxicity. Rifampin can induce hepatic microsomal enzymes, thereby accelerating the metabolism of certain drugs, such as beta-blockers, calciferol, warfarin, cyclosporine, dapsone, diazepam, digitalis, hexobarbital, ketoconazole, methadone, oral contraceptives, oral hypoglycemic agents, phenytoin sodium, sulfasalazine, theophylline, and certain antiarrhythmic drugs, such as disopyramide, lorcainide, mexiletine, quinidine, and verapamil. Rifampin can induce hepatic steroid-metabolizing enzymes, thereby reducing the levels of glucocorticoids and mineralocorticoids. When rifampin is used in combination with chloramphenicol, rifampin will decrease the serum concentration of chloramphenicol. When rifampin is used in combination with oral contraceptives, the efficacy of oral contraceptives will be reduced because rifampin rapidly destroys estrogen and is itself a potent inducer of hepatic metabolic enzymes. There are reports that rifampin used in combination with oral contraceptives may cause certain menstrual disorders. When rifampin is used in combination with corticosteroids, the plasma cortisol half-life is shortened, and the excretion of urinary cortisol metabolites increases. The dose of corticosteroids may need to be doubled or quadrupled. When rifampin is used in combination with cyclosporine, serum cycloserine levels may decrease. In the treatment of leprosy, rifampin may induce the metabolism of dapsone, but this is not clinically significant. Patients taking rifampin and concurrently taking digoxin to treat heart failure may experience a worsening of their clinical condition due to a decrease in digoxin blood concentrations. Therefore, the dose of digoxin may need to be increased. Another cardiac medication used to treat arrhythmias is disopyramide. When used in combination with rifampin, it can decrease the plasma concentrations of antiarrhythmic drugs. The clinical significance of this effect remains to be determined. Patients receiving methadone maintenance therapy to wean off narcotics may experience narcotic withdrawal symptoms if rifampin concomitantly causes a decrease in methadone plasma concentrations. Rifampin may also alter the distribution of methadone. Rifampin induces hepatic enzyme metabolism, thereby reducing metoprolol plasma concentrations, although this effect may not be clinically significant. When rifampin is used in combination with phenytoin sodium, the clearance of phenytoin sodium doubles, significantly reducing the efficacy of antiepileptic drugs. Due to the risk of ventricular arrhythmias, the dose of quinidine needs to be adjusted when used in combination with rifampin. It is recommended that the dose of quinidine be readjusted when rifampin treatment is increased or discontinued. When verapamil is used in combination with rifampin, rifampin induces liver enzymes, thereby accelerating the metabolism of calcium channel blockers and rendering verapamil plasma concentrations undetectable. Rifampin can decrease plasma calciferol (vitamin D) levels by inducing enzyme activity. Barbiturates and salicylates can reduce the activity of rifampin. Clofazimine has a wide range of effects on rifampin, from no effect to reducing its absorption rate, delaying the time to peak plasma concentration, and lowering plasma rifampin concentration. When rifampin is used in combination with ketoconazole, it reduces the therapeutic concentration of ketoconazole. When rifampin is used in combination with oral hypoglycemic agents (tolbutamide and chlorpropamide), the elimination half-life of the latter two drugs is shortened. Rifampin can enhance the antifungal activity of amphotericin B. Probenecid can reduce hepatic uptake of rifampin. Animal/Plant Studies: Carcinogenicity: An increased incidence of liver cancer has been reported in female mice in one mouse strain after one year of administration of rifampin at 2% to 10% of the maximum human dose. Teratogenicity: Cleft palate and spina bifida have been reported in rodents treated with high doses of rifampin daily at 100 to 150 mg/kg body weight. Rifampin is teratogenic in rats and mice. Mutagenicity: Existing mutagenicity studies indicate that rifampin is not mutagenic.
Interactions
The interaction between ethambutol and rifampin (rifampin) may have resulted in a marked Stevens-Johnson syndrome in a 40-year-old male patient with tuberculosis.
Daily alcohol consumption may increase the risk of rifampin-induced hepatotoxicity and accelerate rifampin metabolism; dose adjustment of rifampin may be necessary, and patients should be closely monitored for signs of hepatotoxicity.
Rifampin can increase the metabolism of theophylline, tritheophylline, and aminophylline by inducing hepatic microsomal enzymes, leading to increased theophylline clearance.
Except for isoflurane, prolonged use of liver enzyme inducers before anesthesia may increase the metabolism of anesthetics, thereby increasing the risk of hepatotoxicity.
For more complete data on rifampin interactions (40 items in total), please visit the HSDB records page.

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Non-human toxicity values
Rabbit oral LD50 2.12 g/kg
Rats oral LD50 1.72 g/kg
Mice oral LD50 0.885 g/kg
Hepatotoxicity: After long-term administration to rats (20 mg/kg, orally, once daily for 90 days), serum ALT and AST levels increased by 40%~60% compared to the control group, and mild steatosis appeared in liver tissue. The liver tissue returned to normal 4 weeks after drug withdrawal [1]
-Gastrointestinal toxicity: After oral administration of 25 mg/kg to dogs, nausea and diarrhea occurred in about 25% of cases. No serious gastrointestinal bleeding occurred [2]
-Hematologic toxicity: After oral administration of 50 mg/kg to mice for 30 consecutive days, the white blood cell count decreased from 10×10⁹/L to 6.5×10⁹/L. The platelet count did not change significantly. The platelet count returned to normal 2 weeks after drug withdrawal [1]
- Median lethal dose (LD50): The oral LD50 for mice was 1200 mg/kg, and the intravenous LD50 was 350 mg/kg [2]
- Drug interactions: It can strongly induce the activity of CYP3A4, CYP2C9 and CYP2C19 enzymes; when used in combination with warfarin, digoxin or antiretroviral drugs, it can reduce the plasma concentration of the latter [1]
- Skin reaction: In vitro human skin fibroblast experiments showed that after treatment with 10 μg/mL rifampicin, 5% of the cells underwent apoptosis; clinically, rashes and drug fever are occasionally seen (incidence <3%) [2]

[1]. FASEB J . 2013 Jul;27(7):2713-22.

[2]. J Infect . 2014 Feb;68(2):116-24.

[3]. J Bacteriol . 2000 Nov;182(22):6358-65.

Therapeutic Uses

Antibiotics, anti-tuberculosis drugs; enzyme inhibitors; leprosy treatment drugs; nucleic acid synthesis inhibitors. Rifampin, used in combination with other anti-tuberculosis drugs, is indicated for the treatment of various types of tuberculosis, including tuberculous meningitis. /US Product Label Includes/
Rifampin is indicated for the treatment of close contacts of patients with confirmed or suspected Neisseria meningitidis infection. These close contacts include other family members, children in daycare centers, daycare staff, and closed populations, such as new recruits. Healthcare workers who have had close contact with index cases (e.g., mouth-to-mouth resuscitation) should also receive prophylactic treatment. /US Product Label Includes/
Rifampin is indicated for the treatment of close contacts of patients with confirmed or suspected Haemophilus influenzae type b infection, provided that at least one close contact is 4 years of age or younger. A close contact is defined as someone who has had contact with an index case for 4 hours or more per day for at least 5 days in the last 7 days. /US Product Label Does Not Include/
For more complete data on the therapeutic uses of rifampin (7 types), please visit the HSDB record page.

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Drug Warning
Severe liver injury, including several deaths, has been reported in patients receiving treatment with a regimen containing rifampin and pyrazinamide for latent tuberculosis infection. Between October 2000 and June 2003, the U.S. Centers for Disease Control and Prevention (CDC) received 48 reports of severe liver injury (i.e., hospitalization or death) in patients with latent tuberculosis infection treated with rifampin and pyrazinamide, of whom 11 died. In many of the deaths, liver injury occurred in the second month of the two-month treatment regimen. Some of the deceased patients received the rifampin and pyrazinamide regimen because they had a history of isoniazid-associated hepatitis, and others had chronic liver disease risk factors (e.g., prior serological evidence of hepatitis A or B, idiopathic nonalcoholic steatohepatitis, alcohol or parenteral drug abuse, or concomitant use of other medications associated with specific liver injury). Although data are limited, there is currently no evidence that HIV-infected individuals receiving this treatment regimen have an increased risk of severe hepatitis. Evidence suggests that the incidence of severe liver injury and death from latent tuberculosis infection treated with rifampin and pyrazinamide is higher than that from isoniazid. Based on these reports, rifampin and pyrazinamide regimens should only be used to treat latent tuberculosis infection when the potential benefit outweighs the risk of liver injury and death. Rifampin can cause transient increases in serum AST (SGOT), ALT (SGPT), bilirubin, and alkaline phosphatase levels. Occasionally, asymptomatic jaundice occurs and resolves spontaneously without discontinuation of the drug. However, there have been reports of hepatitis and death associated with jaundice in patients with pre-existing liver disease or those taking other hepatotoxic drugs concurrently. In rare cases, there have been reports of hepatitis or shock-like syndromes (considered anaphylactic reactions) with liver involvement and abnormal liver function test results. Pregnancy risk level: C / Risk cannot be ruled out. Currently, adequate, well-controlled human studies are lacking, and animal studies have not shown any risk to the fetus. Use of this drug during pregnancy may cause harm to the fetus; however, the potential benefit may outweigh the potential risk. Immunosuppressive effects have been observed in some animal studies, but this appears to be clinically insignificant. For more complete data on drug warnings for rifampin (21 in total), please visit the HSDB records page.

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Pharmacodynamics
Rifampin is an antibiotic that inhibits the activity of DNA-dependent RNA polymerase in susceptible cells. Specifically, it interacts with bacterial RNA polymerase but does not inhibit mammalian enzymes. It has bactericidal activity and broad-spectrum antibacterial activity against most Gram-positive and Gram-negative bacteria (including Pseudomonas aeruginosa) and Mycobacterium tuberculosis. Due to the rapid emergence of resistant bacteria, its use is limited to the treatment of mycobacterial infections and a few other indications. Rifampin is well absorbed orally and widely distributed in systemic tissues and fluids, including cerebrospinal fluid. Rifampin is metabolized in the liver and excreted primarily in bile, with a small amount excreted in the urine, but no dose adjustment is required in cases of renal insufficiency. Mechanism of action: Rifampin specifically binds to the β subunit (rpoB) of bacterial RNA polymerase, blocking RNA chain synthesis in the transcription initiation stage, and ultimately inhibiting bacterial gene expression and protein synthesis, thus exerting a bactericidal effect [3] - Indications: Used to treat tuberculosis (in combination with isoniazid, ethambutol, etc.), leprosy, and methicillin-resistant Staphylococcus aureus (MRSA) infection (e.g., sepsis, pneumonia) [2] - Resistance mechanism: Mainly point mutations in the rpoB gene (commonly found in codons 507-533), which lead to changes in the drug binding site of RNA polymerase, thereby reducing the drug binding capacity. Affinity [3] - Precautions for administration: Absorption is better when taken orally on an empty stomach; taking it with food can reduce bioavailability by 10%-15%; long-term use requires regular monitoring of liver function [1] - Use in special populations: Use with caution in pregnant women; breastfeeding women should stop breastfeeding during the use of this drug; patients with liver dysfunction need to reduce the dose [2]

C43H58N4O12

822.94

822.405

C, 62.76; H, 7.10; N, 6.81; O, 23.33

13292-46-1

135398735

Red to orange platelets from acetone
Red-brown crystalline powder

1.3±0.1 g/cm3

1004.4±65.0 °C at 760 mmHg

183ºC (dec.)

561.3±34.3 °C

0.0±0.3 mmHg at 25°C

1.613

1.09

6

15

5

59

1620

9

O(C(C([H])([H])[H])=O)[C@]1([H])[C@]([H])(C([H])([H])[H])[C@]([H])(C([H])=C([H])O[C@]2(C([H])([H])[H])C(C3C4=C(C(/C(/[H])=N/N5C([H])([H])C([H])([H])N(C([H])([H])[H])C([H])([H])C5([H])[H])=C(C(=C4C(=C(C([H])([H])[H])C=3O2)O[H])O[H])N([H])C(C(C([H])([H])[H])=C([H])C([H])=C([H])[C@]([H])(C([H])([H])[H])[C@@]([H])([C@@]([H])(C([H])([H])[H])[C@]([H])([C@@]1([H])C([H])([H])[H])O[H])O[H])=O)O[H])=O)OC([H])([H])[H] |c:18,83,t:79|

JQXXHWHPUNPDRT-WLSIYKJHSA-N

InChI=1S/C43H58N4O12/c1-21-12-11-13-22(2)42(55)45-33-28(20-44-47-17-15-46(9)16-18-47)37(52)30-31(38(33)53)36(51)26(6)40-32(30)41(54)43(8,59-40)57-19-14-29(56-10)23(3)39(58-27(7)48)25(5)35(50)24(4)34(21)49/h11-14,19-21,23-25,29,34-35,39,49-53H,15-18H2,1-10H3,(H,45,55)/b12-11+,19-14+,22-13-,44-20+/t21-,23+,24+,25+,29-,34-,35+,39+,43-/m0/s1

[(7S,9E,11S,12R,13S,14R,15R,16R,17S,18S,19E,21Z)-2,15,17,27,29-pentahydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-26-[(E)-(4-methylpiperazin-1-yl)iminomethyl]-6,23-dioxo-8,30-dioxa-24-azatetracyclo[23.3.1.14,7.05,28]triaconta-1(29),2,4,9,19,21,25,27-octaen-13-yl] acetate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: 2.5 mg/mL (3.04 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (3.04 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)