Interaction between RFP and PAS was reported first in 1970 by Boman et al., however, this suggestion was completely retracted in 1975 by their following investigations; namely it depends on the physical property of the used PAS product, but not on PAS itself. In order to confirm their reports, this study was done by means of multiple determinations of the serum levels of RFP and PAS, and their urinary excretions after the simultaneous oral administration of both drugs. Various PAS products, i.e. PAS-Na xtal, PAS-Na tablet, PAS-Ca granule and PAS-bentonite granule were tested in this investigation. Under the simultaneous administration of 450mg RFP with 10g PAS-Ca granules, RFP absorption was markedly inhibited by PAS in all tested 12 healthy volunteers. The inhibition of RFP absorption by PAS was comfirmed by detailed investigations of the serial urinary excretion of RFP and PAS.The inhibitory action of RFP on the PAS absorption was also observed, however, it was very slight. These results suggest that the absorption of PAS from the alimental tract was much faster than that of RFP, under the competitive absorption of both drugs.The grade of inhibitory action of tested PAS products was highes in PAS-bentonite granule, then PAS-Ca granule, PAS-Na tablet and lowest in PAS-Na xtal. The inhibition of RFP absorption by the dominant fast absorption of PAS seems to be recovered in the following stage, but not completely. This indicates the importance of the active absorption of the drugs in the early stage. In two or three divided doses of 10g PAS-Ca granules, the inhibitory action of PAS was diminished in proportion to the reduced dosage of PAS given with RFP. The PAS absorption from the alimentary tract was very fast irrespective of the PAS products, and the urinary excretion of PAS was also rapid. The content of free PAS in the blood almost disappeared within 4 hours in case of the dosage of one thirds of 10 g PAS-Ca granules, 6 hours in case of 5g dosage, and 8 hours in cace of 10g dosage, respectively. Thus, it must be mentioned that the metabolism of PAS was accelerated with its divided doses, and a single dose of daily PAS might better be recommended. If a single dose of daily PAS is given in combination with RFP, PAS should be given about 2 hours after the administration of RFP, as it is already completely absorbed by this time.
