Experimental and Clinical Studies on Rifacinna® - The New Effective Antituberculous Drug
Dimova V. Res. Inst. Pharmacology, Bulgaria; 2-Shimane Univ. School Med., Izumo, Japan
Abstract:
New antituberculosis drugs are needed for three main reasons: 1) to shorten or simplify treatment of tuberculosis caused by drug-susceptible organisms, 2) to improve treatment of drug-resistant tuberculosis, and 3) to provide more efficient and effective treatment of latent tuberculosis infection.
Development of new drugs from known compounds having already shown safety and efficacy is an attractive strategy from the economical, pharmaceutical and clinical point of view. In a similar manner there has been developed a new rifamycin analogue, 3-(4-cynnamyl-piperazinyl-imino-methyl)- rifamycin SV.
A new rifamycin derivative 3-(4-cinnamyl-piperazinyl iminomethyl) rifamycin SV (T9) and its sodium salt (T11, Rifacinna®) 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 eradication of mycobacteria in experimental generalized tuberculosis.
Pharmacological studies established: excellent pharmacokinetic profile - following single oral dose 10 mg/kg Tmax 5-6 h, Cmax 5-9 mg/L, T 1/2 33-34 h; low toxicity; no teratogenic and embryotoxic effects.
The clinical study of Rifacinna shows shorter course of treatment, higher therapeutic efficacy than rifampicin in patients with infiltrative, disseminated and cavitary form of pulmonary tuberculosis, good tolerability and safety profile.
Keywords: tuberculosis, rifamysins, Rifacinna, T9, T11, Mycobacterium tuberculosis, in vitro, in vivo, pharmacokinetics, experimental tuberculosis, toxicology, clinicaln study.
