title: Experimental and clinical studies on Rifacinna--the new effective antituberculous drug (review).
abstract: 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.
authors.affiliation: Res. Inst. Pharmacology, Bulgaria. vdimova@actavis.bg
authors.forename: Dimova
authors.initials: D
authors.lastname: Velichka
authors.forename: Atanasova
authors.initials: A
authors.lastname: Ivana
authors.forename: Tomioka
authors.initials: T
authors.lastname: Haruaki
authors.forename: Sato
authors.initials: S
authors.lastname: Katsumasa
authors.forename: Reddy
authors.initials: R
authors.lastname: Venkata
authors.forename: Geeta
authors.initials: G
authors.lastname: Nadadhur
authors.forename: Daneluzzi
authors.initials: D
authors.lastname: Donna
authors.forename: Kantardjiev
authors.initials: K
authors.lastname: Todor
authors.forename: Dhople
authors.initials: D
authors.lastname: Arvind
authors.forename: Feschenko
authors.initials: F
authors.lastname: Yurii
authors.forename: Yashina
authors.initials: Y
authors.lastname: Ljudmila
authors.forename: Andrei
authors.initials: A
authors.lastname: Toumanov
authors.forename: Zhivkova
authors.initials: Z
authors.lastname: Zvetana
authors.forename: Sano
authors.initials: S
authors.lastname: Chiaki
mesh_terms: 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
chemical_list: D000904:Antibiotics, Antitubercular; D012294:Rifamycins; C023808:rifamycin SV