Rifampicin Aminosalicylates

Antimycobacterials and related drugs Aminosalicylic acid (PAS), Capreomycin, Clofazimine, Cycloserine, Dapsone, Ethambutol, Ethionamide, Isoniazid, Methaniazide, Protionamide, Pyrazinamide, Rifabutin, Rifampicin (Rifampin), Rifamycin, Rihipentine, Rihiximin... 

Boman G. Serum concentration and half-life of rifampicin after simultaneous oral administration of aminosalicylic acid or isoniazid EurJ Clin Pharmacol ( 974) 7, 217-25. 

The serum levels of rifampicin are approximately halved if aminosalicylic acid granules containing bentonite are given. 

In 30 patients with tuberculosis the serum levels of rifampicin 10 mg/kg were reduced by more than 50%, from 6.06 to 2.91 micrograms/mL, at 2 hours by aminosalicylate. Later studies in 6 healthy subjects showed that this interaction was not due to the aminosalicylic acid itself but to the bentonite, which was the main excipient of the granules. The rifampicin AUC was statistically unchanged in the presence of sodium aminosali-... 

Other studies confirm this marked reduction in serum rifampicin levels in the presence of bentonite in aminosalicylic acid granules. ... 

The bentonite excipient in the aminosalicylic acid granules adsorbs the rifampicin onto its surface so that much less is available for absorption, which results in reduced serum levels. Bentonite is a naturally occurring mineral (montmorillonite) consisting largely of hydrate aluminium silicate, and is similar to kaolin. 

Boman G, BorgaO,HanngrenA, Malmborg A-S and Sjoqvist F. Pharmacokinetic irileractioiis between the tuberculostatics rifampicin, para-aminosalicylic acid and isoniazid Acta Pharmacol Toxicol (Copenh) (1970) 28 (Suppl 1), 15. 

Ampicillin and rifampicin markedly reduce the colonic release of 5-aminosalicylate (the active drug) from sulfasalazine. Metronidazole appears not to interact adversely with sulfasalazine. 

Berte SJ, Di Mase ID, Christianson CS (1964) losoniazid para-aminosalicylic acid and streptomycin intolerance in 1,714 patients. Am Rev. Respir Dis 90 598-606 Blajchman MA, Lowry RC, Pettit JE, Stradling P (1970) Rifampicin-induced immune thrombocytopenia. Br Med J 3 24-26... 

An interesting and unusual adverse effect attributed to pyrazinamide was described in a paper from the United States (54 ). A patient was described who suffered several attacks of acute intermittent porphyria whilst under treatment for tuberculosis. The first attack occurred after 18 months therapy with isoniazid and ethambutol. The second episode occurred after 14 days treatment with rifampicin, 7 days treatment with pyrazinamide and 3 days treatment with streptomycin. The patient was subsequently treated successfully with a combination of rifampicin, ethambutol and capreomycin. The compounds were investigated for their capacity to induce hepatic delta-aminolaev-ulinic acid synthesis in an in vitro preparation of rat Uver. The results showed that pyrazinamide had a greater potential for inducing the enzyme activity than any of the other compounds. It is worthy of note, however, that in this in vitro system para-aminosalicylic acid, rifampicin, cycloserine and ethionamide all induced increased delta-aminolaevulinic acid synthesis. 

---