The Japanese Journal of Antibiotics

The absorption, distribution, metabolism and excretion of RFP have been studied in rats using radioisotope technique. Orally administered drug reached maximum blood levels 2.45×10⁵ and 5.30×10 dpm/ml in high and low doses at 8 hours, respectively.
The maximum levels of radioactivity in all organs except liver were observed 8 hours after administration in the blood. The liver level reached a maximum 2 hours after administration and this level was maintained until 24 hours. The radioactivity was the highest in the liver, then it decreased in the order of kidney>lung>heart>spleen.
In male rats, 21.3% of the radioactivity was recovered in the urine and 40.6% in the feces by 48 hours after a high dose. Biliary excretion of RFP reached about 6.6% within 8 hours after administration.
Two kinds of metabolite were found in the liver, bile and feces. The metabolites were identified to be 25-desacetylrifampicin and N-desmethylrifampicin in comparison with authentic samples.

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Several supplementary investigations were performed on rifampicin with the following results.
1. Successive oral administrations of rifampicin in dose of 300mg two times daily for 8 days were continued in 4 healthy volunteers. Serum levels were determined four times daily at times prior to each dosing and after 2 hours of each administration. The results showed no accumulation of drug in the serum through the whole observation period.
2) Rifampicin was administered in the fasting time or after breakfast to 5 healthy volunteers by cross-over method, and serum levels and urinary recoveries were compared. The peak serum level appeared rather earlier and higher in the former accompanying with considerable lower rate of urinary recovery.
3) As a solvent of rifampicin to prepare a standard curve, dimethylsulfoxide seemed to have less effect on bioassay procedure than dimethylformamide which has been used widely.

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In the study of therapeutic effect of experimental infections and distribution of kujimycins A and B in urine, blood and organs in mice, the following results were obtained.
1. Kujimycins A and B exhibited a CD₅₀ of 50mg/kg×5 against intraperitoneal staphylococcal infection in mice, but they did not show the therapeutic effect at less than 25mg/kg×5.
2. In subcutaneous staphylococcal infection in mice with 10⁸ cells inoculation of St. aureus 226 strain, kujimycins A and B showed about 50% abscess suppressing effect by 375mg/kg administration of single oral dose. In the infection with 5×10⁷ cells inoculation, kujimycins A and B showed about 70% abscess suppressing effect by 250mg/kg single oral administration.
3. In subcutaneous streptococcal infection in mice with 5×10⁷ cells Streptococcus hemolyticus 1655, kujmycins A and B showed about 50% abscess suppressing effect by 375mg/kg single oral administration.
4. In the study of distribution of kujimycins A and B in urine, blood and organs, the highest activity were found in liver and kidney among the organs except blood and urine.
5. Kujimycins A and B were not inactivated by liver homogenate, and they were stable for long period.

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