Mechanism of the inhibitory effect of PAS granules on the absorption of rifampicin: adsorption of rifampicin by an excipient, bentonite.
The bioavailability (plasma concentrations, AUC and urinary excretion) of an oral solution of rifampicin was investigated in six healthy volunteers. Simultaneous administration of PAS granules produced a significant decrease in the absorption of RMP, whereas Na-PAS tablets had no effect. This indicated that the dosage form of the granules and not PAS itself was responsible for the interaction, and that the dissolution of RMP was not involved. The interaction could be reproduced by giving dummy granules that contained the same excipients but no PAS. The disintegration and dissolution of PAS granules in vitro correlated well with the disappearance of RMP from the solution. The major excipient of the granules, bentonite (a mineral closely related to kaolin), was found to adsorb rifampicin rapidly and strongly.
D000327:Adsorption; D000328:Adult; D000636:Aminosalicylic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D001546:Bentonite / Q000494:pharmacology*; D001681:Biological Assay; D001682:Biological Availability; D005079:Excipients; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D012293:Rifampin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012505:Sarcina / Q000187:drug effects; D012995:Solubility
D000636:Aminosalicylic Acids; D005079:Excipients; D001546:Bentonite; D012293:Rifampin