Since Lehmann reported PAS as the chemotherapeutic for tuberculosis in 1946, oral administration of PAS for the treatment of tuberculosis is being widely practiced. However, it is well known that the administration had to be suspende on some occasions due to general intoxication phenomenon especially due to gastroenteric symptoms. Several improved methods for the administration have been published since then. Barclay and Boger claimed that when isotonic solution of the sodium salt of PAS is injected intravenously, the side reaction is relatively mild although the blood level is considerably high. Further, Rieber et al. tried out the rectal application of PAS on the patients, and comparatively investigated the results of oral administration and rectal application in the case when it is administered alone.
On the occasion when the author conducted the experiments on the administration of PAS combined with other substances, he attempted to investigate the combination with the substances, which he and his coworkers employed in their previous work on the rectal application of penicillin.
The author employed rabbits as experimental animals, and conducted experiments on the absorption of PAS in the colon. In the case when PAS alone was orally administered, PAS content in the plasma reached the maximum 1 hour after the administration, and diminished as the time passed. When PAS alone was administered as enema, the content in the plasma reached the maximum 30-60 minutes after the administration, and diminished as the time goes on similarly to the case of oral administration.
When PAS was administered as enema in combination with dextrose, glycocoll and chloral hydrate, the plasma level of PAS reached the maximum 30 minutes after the administration, and became relatively low after 2-4 hours. In the case of the combination with dextrose, taurin and chloral hydrate, the plasma level of PAS reached the maximum after 1 hour, and relatively high level was maintained even after 2 hours. In the case of the combination with chloral hydrate alone, the plasma level after 30 minutes was the highest, and the level went down gradually. However, even after 6 hours, it maintained the effective level. When PAS was administered in combination with urethane, the plasma level of PAS after 30 minutes was the highest, and it diminished gradually. Contrary to this, when PAS was administered in combination with cattle bile or hog bile respectively, the plasma level of PAS demonstrated the highest after 30 minutes. Even after 4 hours, relatively high plasma level was recognized.
Previously, when the author and his coworkers conducted experiments on the absorption of penicillin in the colon, they gave penicillin alone as well as combined with dextrose, glycocoll, taurin, chloral hydrate, morphine, magnesium sulfate, Sprase, urethane, cattle bile or hog bile as combined enema. In the case of penicillin, the absorption was extremely promoted when it was administered in combination with urethane. The blood level was found very high and maintained longer compared with the combination with other substances. However, in the case of the combination with bile (cattle and hog), it was learnt that, although the blood level was found high, penicillin disappears relatively rapidly from the blood occasionally. PASS is different from penicillin in this respect.
The author is conducting further investigations in pursuit of even more suitable substances for the application of PAS in the colon.