Rifapentine inhibits bacterial RNA synthesis by binding to the β-subunit of DNA-dependent RNA polymerase in susceptible species. Rifapentine is generally more active than rifampicin against sensitive strains of M. tuberculosis. Rifapentine significantly increases the rate of antipyrine and pentobarbital metabolism in vivo. Rifapentine also increases liver weight, the content of liver microsomal protein and cytochrome P-450, the activity of NADPH-cytochrome C reductase and NADPH oxidase. Rifapentine combined with isoniazid (INH) and pyrazinamide (PZA) administered daily results in an apparent clearance of M.tuberculosis organisms in the lungs and spleens of infected mice after 10 weeks of treatment

Absorption, Distribution and Excretion
Rapid and adequate absorption from the gastrointestinal tract. Following a single oral dose of 600 mg of radiolabeled rifapentine in healthy volunteers (n=4), 87% of the 14C-labeled rifapentine was recovered from urine (17%) and feces (70%). 70.2 ± 9.1 L Apparent oral clearance = 2.51 ± 0.14 L/h [male tuberculosis patients treated with 600 mg rifapentine in combination with isoniazid, pyrazinamide, and ethambutol] Apparent oral clearance = 1.69 ± 0.41 L/h [female tuberculosis patients treated with 600 mg rifapentine in combination with isoniazid, pyrazinamide, and ethambutol] [ethambutol] Metabolisms/Metabolites Liver

Hepatotoxicity
Due to the limited use of rifapentine, its effects on the liver are not as well-defined as those of rifampin, but may be similar. Therefore, long-term use of rifapentine can lead to mild, transient increases in serum transaminase levels in 2% to 7% of patients; these abnormalities usually do not require dose adjustment or discontinuation. There are currently no reports of clinically significant liver injury caused by rifapentine, but its potential to cause acute liver injury may be similar to that of rifampin. Because rifapentine is often used in combination with isoniazid and/or pyrazinamide (two other known hepatotoxic drugs), the cause of acute liver injury in patients treated with rifapentine may be difficult to determine as being caused by a single drug; some evidence suggests that these combination therapies are more likely to cause liver injury than either drug alone. Typically, rifamycin-induced liver injury develops within 1 to 6 weeks, with an initial serum enzyme profile that is usually hepatocellular, but unlike isoniazid and pyrazinamide, cholestatic and mixed patterns may also occur. Extrahepatic manifestations of rifapentine hepatotoxicity, such as fever, rash, arthralgia, edema, eosinophilia, and autoantibody formation, are uncommon. Rifapentine has not been proven to be hepatotoxic. Probability score: E (Unproven, but suspected cause of clinically significant liver injury). Pregnancy and Lactation Use ◉ Overview of Lactation Use
The amount of rifapentine and its metabolites in breast milk is insufficient to treat tuberculosis in breastfed infants. The US Centers for Disease Control and Prevention and other professional agencies state that women taking rifapentine should not be discouraged from breastfeeding. Infants should be monitored for signs of hepatotoxicity. Breast milk may appear reddish-orange. ◉ Effects on Breastfed Infants
No published information found as of the revision date. ◉ Effects on Lactation and Breast Milk
No published information found as of the revision date.

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Protein binding rate
97.7% (bound to plasma proteins)

Ann Pharmacother.1999 Nov;33(11):1203-10;Antimicrob Agents Chemother.1995Sep;39(9):2073-7;Drugs.1998 Oct;56(4):607-16; discussion 617.

Rifapentine is an N-alkylpiperazine, N-iminopiperazine compound belonging to the rifamycin class. It is an anti-tuberculosis drug and a treatment for leprosy. Rifapentine is a prescription antibacterial drug approved by the U.S. Food and Drug Administration (FDA) for the treatment of active pulmonary tuberculosis (also known as tuberculosis). Rifapentine is also FDA-approved for the treatment of latent tuberculosis infection to prevent the development of active tuberculosis. Tuberculosis can be an opportunistic infection of HIV. Rifapentine is an antibiotic used to treat tuberculosis. It works by inhibiting the activity of DNA-dependent RNA polymerase in susceptible cells. Specifically, it interacts with bacterial RNA polymerase but does not inhibit mammalian enzymes. Rifapentine is a rifamycin-based antimycobacterial drug. Rifapentine is a rifamycin antibiotic with a structure and activity similar to rifampin and rifabutin, and is often used in combination with other drugs to treat tuberculosis, especially with once-weekly or twice-weekly dosing regimens. Rifapentine is associated with transient and asymptomatic elevations in serum transaminases, which may be one of the causes of clinically apparent acute liver injury. Rifapentine is a long-acting cyclopentyl-substituted derivative of rifamycin, used to treat mycobacterial infections. See also: Rifapentine hydrochloride (its active ingredient). Indications: For the treatment of pulmonary tuberculosis. Mechanism of Action: Rifapentine has high antibacterial and bactericidal activity, particularly effective against bacteria growing within macrophages derived from human monocytes. Rifapentine inhibits DNA-dependent RNA polymerase in susceptible strains of Mycobacterium tuberculosis. Rifapentine works by inhibiting DNA-dependent RNA polymerase, leading to RNA synthesis inhibition and cell death. Pharmacodynamics: Rifapentine 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 RNA polymerase. 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 after oral administration and widely distributed in tissues and fluids throughout the body, including cerebrospinal fluid. It is metabolized in the liver and excreted primarily via bile, with a small amount excreted in the urine; however, no dose adjustment is necessary for patients with renal insufficiency.

C47H64N4O12

877.03

876.452

C, 64.37; H, 7.36; N, 6.39; O, 21.89

61379-65-5

Rifapentine-d9

135403821

Solid powder

1.4±0.1 g/cm3

969.3±65.0 °C at 760 mmHg

179-180ºC

540.0±34.3 °C

0.0±0.3 mmHg at 25°C

1.625

2.58

6

15

6

63

1730

9

OC(C1=C(C2=O)C(O[C@@]2(O/C=C/[C@@H]([C@H]([C@@]([C@@H]3C)([H])OC(C)=O)C)OC)C)=C(C)C(O)=C1C(O)=C4NC(/C(C)=C\C=C\[C@@H]([C@@H]([C@@H](C)[C@H]3O)O)C)=O)=C4/C=N/N5CCN(C6CCCC6)CC5

WDZCUPBHRAEYDL-GZAUEHORSA-N

InChI=1S/C47H64N4O12/c1-24-13-12-14-25(2)46(59)49-37-32(23-48-51-20-18-50(19-21-51)31-15-10-11-16-31)41(56)34-35(42(37)57)40(55)29(6)44-36(34)45(58)47(8,63-44)61-22-17-33(60-9)26(3)43(62-30(7)52)28(5)39(54)27(4)38(24)53/h12-14,17,22-24,26-28,31,33,38-39,43,53-57H,10-11,15-16,18-21H2,1-9H3,(H,49,59)/b13-12+,22-17+,25-14-,48-23+/t24-,26+,27+,28+,33-,38-,39+,43+,47-/m0/s1

3-(N-(4-Cyclopentyl-1-piperazinyl)formimidoyl)rifamycin

2934.99.03.00

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)

DMSO : 50 ~100 mg/mL ( 57.01 ~114.02 mM )
H2O : ~0.67 mg/mL (~0.76 mM)
Ethanol : ~10 mg/mL

Solubility in Formulation 1: ≥ 2.5 mg/mL (2.85 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% 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 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: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: ≥ 2.5 mg/mL (2.85 mM)

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