[A 50-year year history of new drugs in Japan: the developments of antituberculosis drugs and their influences on the epidemiological aspects].

Drugs used in the treatment of tuberculosis (Tb) in Japan are investigated. Especially the chemotherapy for Tb and its influences on epidemiological aspects are discussed. 1. Various drugs were used for Tb patients before the World War II, but none was effective in curing this infectious disease. Creosote and guajacol groups were used frequently to relieve symptoms of pulmonary tuberculosis, but the disease could not cure itself. Because of the sacrifice of young patients, the mortality rate of Tb from 1935 to 1950 was ranked as the worst in Japan. So until the advent of chemotherapeutic drugs, Tb was known as the most formidable fatal plague. 2. Streptomycin (SM), the first effective chemotherapeutic drug, was imported into Japan and widely used from 1947. PAS in 1950 and isoniazid (INH) in 1952 were introduced to Tb therapy. The triple combination therapy of these drugs was considered the most favorable regimen for Tb from the 1950s to the early 1970s. Excellent results were obtained in this period. The mortality rate of Tb had dropped rapidly from its peak to half in 1952 and to a fourth in 1956 (Figs. 2, 3). 3. Several anti-Tb drugs, such as pyrazinamide ethionacide, ethambutol, and some antibiotics (kanamycin, cyloserine, and capreomycin) had been discovered and used in practice. These were not used singly, because of their weak clinical efficacies and severe side effects. They were mostly used to prevent the development of bacillus resistance to SM or INH. In the guidelines of the Japanese Society for Tuberculosis, in 1974. drugs used for Tb could be divided into two major categories: first-line and second-line groups. The second-line drugs included those that prevent a high resistance to the main (first-line) drugs. 4. Rifampicin (RFP), the most valuable drug for Tb, was introduced in therapy in Japan in 1971. RFP has a low incidence of severe side-effects, but because of the rapidity with which resistance may develop, it cannot be used alone. RFP in combination with INH is the most effective therapy for all forms of the disease. The guidelines, newly proposed in 1986 by the Japanese Society for Tuberculosis recommended the short 6-month course of treatment that used combination of RFP and INH. The advent of RFP had contributed to the cure of the individual patient, but it did not effect the mortality or the morbidity rate of Tb. Chemotherapy is the most effective means of suppressing tuberculosis, which was formerly nearly always fatal, but it could not completely eradicate the disease. Preventing the development of resistance to chemotherapeutic drugs might be a special problem.