Rifapentine Chemical Properties

Melting point:

179-1800C

Boiling point:

969.3±65.0 °C(Predicted)

Density 

1.35±0.1 g/cm3(Predicted)

storage temp. 

Sealed in dry,Store in freezer, under -20°C

solubility 

methanol: soluble2mg/mL, clear, red to red-brown

form 

powder

pka

4.81±0.70(Predicted)

color 

Red

Safety Information

Hazard Codes 

Xi

Risk Statements 

36/37/38

Safety Statements 

26

WGK Germany 

3

RTECS 

JQ0902000

HS Code 

2941.90.3000

Toxicity

LD50 in mice (mg/kg): >2000 orally; 750 i.p. (Cricchio); LD50 in mice (mg/kg): 3300 orally; 710 i.p. (Aroli)

MSDS

• Language:English Provider:3{[(4-Cyclopentyl-1-piperazinyl)imino]methyl}rifamycin

Rifapentine Usage And Synthesis

Description

Rifapentine is a broad spectrum antibiotic highly active against Gram-positive bacteria and Neisseria gonorrhoea. It is reported to be 10 times more active than the structurally related rifampicin against Mycobacrerim fuberculosis. Unlike rifampicin the bioavailability of rifapentine is significantly increased when administered after a meal.

Chemical Properties

Crystalline Solid

Originator

Shanghai No. 5 Factory (China)

Uses

antibacterial (tuberculostatic);'inhibits DNA-dependent RNA polymerase in susceptible strains of Mycobacterium tuberculosis

Uses

PDE5 inhibitor for erectile dysfunction A semisynthetic ansamycin antibiotic, cyclopentyl derivative of Rifamycin. Treatment of pulmonary tuberculosis

Uses

Semi-synthetic rifamycin. Antibacterial (tuberculostatic)

Definition

ChEBI: Rifapentine is a N-alkylpiperazine, a N-iminopiperazine and a member of rifamycins. It has a role as an antitubercular agent and a leprostatic drug.

Indications

Rifapentine is an analogue of rifampin that is active against M. tuberculosis and M. avium. Rifapentine’s mechanism of action, cross-resistance, hepatic induction of P450 enzymes, drug interactions, and toxic profile are similar to those of rifampin. It has been used in the treatment of tuberculosis caused by rifampinsusceptible strains.

brand name

Priftin (Sanofi Aventis);Rifampin.

Antimicrobial activity

Activity is similar to that of rifampicin, but it is more active against atypical mycobacteria, especially the M. avium complex (MIC <0.06–0.5 mg/L). It has good activity on staphylococci and streptococci (MIC 0.01–0.5 mg/L), L. monocytogenes and Brucella spp.; less against Enterococcus faecalis (MIC 1–4 mg/L). Bacteroides spp. are inhibited by 0.5–2 mg/L. Gram-negative cocci are susceptible and, although some Gram-negative bacilli are inhibited by 4–32 mg/L, most are resistant.

Hazard

Moderately toxic by ingestion.

Pharmaceutical Applications

An analog of rifampicin in which a cyclopentyl group is substituted for a methyl group on the piperazine ring. It is available for oral administration.

Mechanism of action

Because relapse and the emergence of resistant strains of bacteria are associated with poor patient compliance, reduced dosing is expected to increase compliance. Initial clinical studies actually showed that the relapse rates in patients treated with rifapentine (10%) were higher than those in the patients treated with RIF (5%). It was found that poor compliance with the nonrifamycin antituberculin agents was responsible for the increased relapse.

Pharmacokinetics

Oral absorption：c. 70%
C_max600 mg oral ：12 mg/L after 5 h
Plasma half-life：13 h
Volume of distribution：1.5 L/kg
Plasma protein binding：97%
absorption
The absolute oral bioavailability of rifapentine has not been determined. The relative bioavailability of capsules (with an oral solution as reference) is 70%. Food increases absorption: a 600 mg dose taken after a meal gives Cmax and AUC values 44% higher than under fasting conditions. The extended halflife provides therapeutic concentrations for at least 72 h after administration, allowing less frequent dosing.
Distribution
Animal data suggest that it is well distributed in the body, with tissue concentrations exceeding the plasma concentration, except in bone, testes and brain. The ratio of intracellular:extracellular concentration in macrophages was estimated as 24:1.
Metabolism
The main metabolite is an antimicrobially active 25-desacetyl derivative. Although it induces liver cytochromes it is not an inducer of its own metabolism, which is mediated by an esterase. The peak concentration of 25-desacetyl rifapentine is about one-third of that of the unchanged drug, and is attained after about 11 h.
excretion
The main route of elimination is through the bile. In healthy volunteers about 70% of a 600 mg dose of 14C rifapentine was recovered in the feces, and less than 17% in the urine. There is evidence of enterohepatic recycling in humans.

Clinical Use

Tuberculosis (in combination with other antituberculosis drugs)

Side effects

Signs of teratogenic effects and fetal toxicity have been observed when administered during pregnancy to rats and rabbits. Rifapentine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
The most common adverse effect observed in combinations with other antimycobacterial agents was hyperuricemia, most probably due to pyrazinamide. Effects likely to be due to rifapentine were neutropenia (3.7% of patients) and hepatitis (increased transaminases in 1.6% of patients).

in vitro

the activities of rifampin and rifapentine against mycobacterium tuberculosis residing in human monocytederived macrophages were determined. the mic and mbc of rifapentine for intracellular bacteria were two- to four-fold lower than those of rifampin. for extracellular bacteria, this difference was less noticeable. [1].

in vivo

once-a-week exposure to rifapentine concentrations equivalent to that attained in blood after one 600-mg dose resulted during the first week in a dramatic decline in the number of bacteria, and such decline was maintained at a minimal level for a period of four weeks. the prolonged effect of rifapentine found may be associated with high ratios of intracellular accumulation, which were four- to fivefold higher than those found for rifampin [1].

References

[1] mor n, simon b, mezo n, heifets l. comparison of activities of rifapentine and rifampin against mycobacterium tuberculosis residing in human macrophages. antimicrob agents chemother. 1995 sep;39(9):2073-7.
[2] temple me, nahata mc. rifapentine: its role in the treatment of tuberculosis. ann pharmacother. 1999 nov;33(11):1203-10.

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