Zcure Mechanism of Action

Microbiology: Antimicrobial Action: Pyrazinamide has a bactericidal effect against Mycobacterium tuberculosis but appears to have no activity against other Mycobacteria or microorganisms in vitro. The MIC for M. tuberculosis is >20 mcg/mL at pH 5.6. It is almost completely inactive at neutral pH. Pyrazinamide is effective against persisting tubercle bacilli within the acidic intracellular environment of the macrophages. The initial inflammatory response to chemotherapy increased the number of organisms in the acidic environment. As inflammation subsides and pH increases, the sterilizing activity of pyrazinamide decreases. This pH-dependent activity explains the clinical effectiveness of pyrazinamide as part of the initial 8-week phase in short-course treatment regimens. In order to avoid inducing bacterial resistance when used alone, pyrazinamide should always be given together with other antituberculous drugs.
Pharmacokinetics: Pyrazinamide is readily absorbed from the GI tract. Peak serum concentrations occur about 2 hrs after an oral dose and have been reported to be about 35 mcg/mL after 1.5 g and 66 mcg/mL after 3 g. Pyrazinamide is widely distributed in body fluids and tissues and diffuses into the CSF. The t_½ has been reported to be about 9-10 hrs. It is metabolized primarily in the liver by hydrolysis to the major active metabolite pyrazinoic acid which is subsequently hydroxylated to the major excretory product 5-hydroxypyrazinoic acid. It is excreted through the kidney mainly by glomerular filtration. About 70% of a dose appears in the urine within 24 hrs mainly as metabolites and 4-14% as unchanged drug. Pyrazinamide is excreted in breast milk.