Experimental and clinical studies on Rifacinna--the new effective antituberculous drug (review).
Experimental and clinical studies on Rifacinna--the new effective antituberculous drug (review).
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DOI：
10.2174/157489110790112572
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发表时间：
2010
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通讯作者：
Dimova Velichka;Atanasova Ivana;T. Haruaki;Sato Katsumasa;Reddy Venkata;G. Nadadhur;Daneluzzi Donna;Kantardjiev Todor;D. Arvind;F. Yurii;Yashina Ljudmila;Andrei Toumanov;Zhivkova Zvetana;Sano Chiaki
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文献类型：
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作者：
Dimova Velichka;Atanasova Ivana;T. Haruaki;Sato Katsumasa;Reddy Venkata;G. Nadadhur;Daneluzzi Donna;Kantardjiev Todor;D. Arvind;F. Yurii;Yashina Ljudmila;Andrei Toumanov;Zhivkova Zvetana;Sano Chiaki
以利福平、利福喷丁、利福平、利福平为对照，对新的利福霉素衍生物3-(4-肉桂基-哌嗪基亚氨甲基)利福霉素SV(T9)及其钠盐(T11，Rifacinna(R))进行了体外、体内、毒理和临床研究。我们的实验表明，Rifacinna对革兰氏(+)、革兰氏(-)需氧、厌氧病原菌和分枝杆菌具有良好的体外抗菌活性。Rifacinna对葡萄球菌、链球菌有明显的抑制作用。包括耐甲氧西林金黄色葡萄球菌(MIC90-0.06-0.5 mg/L)，对革兰氏(+)、革兰氏(-)厌氧菌(MIC900.5-1 mg/L)，对结核分枝杆菌(MIC90 0.062 mg/L)，耐多药结核分枝杆菌(25%-30%)和禽型分枝杆菌复合菌(MIC0.6-1.0 mg/L)，对革兰氏阳性菌有较高的吞噬活性(0.06~0.125 mg/L)。单次每日剂量10 mg/kg可完全根除实验性全身结核中的分枝杆菌。药理研究表明：单次口服10 mg/kg Tmax 5~6h，C(Max)5~9 mg/L，t1/2 33~34h，药动学曲线良好，毒性低，无致畸和胚胎毒性作用。临床研究表明，利福平治疗浸润型、播散型和空洞型肺结核的疗效高于利福平，耐受性好，安全性好。在这篇综述文章中讨论了一些与结核病治疗有关的最新专利。
A new rifamycin derivative 3-(4-cinnamyl-piperazinyl iminomethyl) rifamycin SV (T9) and its sodium salt (T11, Rifacinna((R))) were in vitro, in vivo, toxicologically and clinically investigated in comparison with rifampicin, rifapentine, rifabutin, rifalazil. Our experiments showed that Rifacinna exhibits excellent in vitro activity against Gram(+), Gram (-) aerobic, anaerobic pathogens and mycobacteria. Rifacinna is active against Staphylococcus, Streptococcus spp. including MRSA, with MIC90- 0.06-0.5 mg/L; against Gram(+), Gram (-) anaerobes with MIC90 0.5 - 1 mg/L; against Mycobacterium tuberculosis (MTB) with MIC90 0.062 mg/L; against MDR resistant MTB (25%-30 %) and Mycobacterium avium complex (MAC) strains with MICs 0.6-1.0 mg/L. It shows high intraphagocytic activity against MAC strains (0.06 0.125mg/L). Single daily dose 10 mg/kg provides complete erradication of mycobacteria in experimental generalized tuberculosis. Pharmacological studies established: excellent pharmacokinetic profile following single oral dose 10mg/kg Tmax 5-6 h, C(max) 5-9 mg/L, T1/2 33-34 h; low toxicity; no teratogenic and embryotoxic effects. The clinical study of Rifacinna shows higher therapeutic efficacy than Rifampicin in patients with infiltrative, disseminated and cavitary form of pulmonary tuberculosis, good tolerability and safety profile. Some of the recent patents related to the treatment of tuberculosis are discussed in this review article.