リファペンチン 化學(xué)特性,用途語,生産方法
外観
うすい黃色～褐色粉末～結(jié)晶
効能
抗生物質(zhì), RNAポリメラーゼ阻害薬
説明
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.
化學(xué)的特性
Crystalline Solid
使用
Semi-synthetic rifamycin. Antibacterial (tuberculostatic)
適応癥
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.
抗菌性
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.
危険性
Moderately toxic by ingestion.
応用例（製薬）
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.
作用機(jī)序
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.
薬物動(dòng)態(tài)學(xué)
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.
DistributionAnimal 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.
MetabolismThe 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.
excretionThe 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.
臨床応用
Tuberculosis (in combination with other antituberculosis drugs)
副作用
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).
リファペンチン 上流と下流の製品情報(bào)
原材料
準(zhǔn)備製品