Experimental and clinical studies on Rifacinna--the new effective antituberculous drug (review).
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.
Velichka
Dimova
D
Res. Inst. Pharmacology, Bulgaria. vdimova@actavis.bg
Ivana
Atanasova
A
Haruaki
Tomioka
T
Katsumasa
Sato
S
Venkata
Reddy
R
Nadadhur
Geeta
G
Donna
Daneluzzi
D
Todor
Kantardjiev
K
Arvind
Dhople
D
Yurii
Feschenko
F
Ljudmila
Yashina
Y
Toumanov
Andrei
A
Zvetana
Zhivkova
Z
Chiaki
Sano
S
D000818:Animals; D000904:Antibiotics, Antitubercular / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D004195:Disease Models, Animal; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009161:Mycobacterium / Q000187:drug effects* / Q000472:pathogenicity; D012294:Rifamycins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D013329:Structure-Activity Relationship; D018675:Toxicity Tests; D016896:Treatment Outcome; D014376:Tuberculosis / Q000188:drug therapy* / Q000382:microbiology
D000904:Antibiotics, Antitubercular; D012294:Rifamycins; C023808:rifamycin SV