[Status quo of pyrazinamide as an antituberculosis drug]

Pyrazinamide (PZA), an antituberculosis agent, was first synthesized in 1940 by Hall and Spoerri and a clinical trial was carried out since 1949 by Yeager and others. Its usefulness as a potent antituberculosis drug was first reported by them in 1952. PZA was once believed to be a secondary choice drug for cases with refractory tuberculosis and/or relapsed cases which are resistant to all other antituberculosis drugs. There was some hesitation among doctors to use PZA for the initial treatment of tuberculosis because of rather high incidence of liver impairment after the use of regimens with PZA. It was, however, revealed later that this was not always true as PZA was ordinarily employed for clinical use in combination with ethionamide and/or cycloserin, and the latter drugs are both known to be hepatotoxic, too. PZA has a unique biological activity observed in murine experimental tuberculosis. The study showed that PZA when administered to animals, enters into the bacilli-ingested macrophages and exerts its killing effect on the bacilli under the environment of acidic pH inside the phagosome of the cells and in areas of acute inflammation both of which favors the acid-fast bacilli to stay in a dormant state and proliferate very slowly. This unique killing ability of PZA which is deficient in other drugs has recently spotlighted PZA once again as a pivotal and first line agent for the 6 months short course chemotherapy of tuberculosis. Sterile eradication of microbe is indispensable for the chemotherapy of tuberculosis, and the potency of a certain antituberculosis agent could be assessed by the availability of negative conversion of bacilli in sputum by culture within two months of administration of the drug. Another important aspect to assess the potency of a drug is to observe the relapse rate after the termination of therapy with the drug. The addition of PZA to the ordinary regimen consisting of INH, RFP and SM/EB has been reported to raise the negative conversion rate of bacilli from 60-70% by the regimen without PZA to as high as 80-90% by the regimen with PZA. In addition, there is no difference in the relapse rate of about 0-2% within 2 years after the termination of chemotherapy between the two regimens; 6 months with PZA and 9 months without PZA. Thus, the addition of PZA to the ordinary regimen enabled us to shorten the duration of antituberculosis chemotherapy than before.(ABSTRACT TRUNCATED AT 400 WORDS)