Study of the interaction between rifapentine and isoniazid under acid conditions

Journal of Pharmaceutical and Biomedical Analysis
Bhagwat PrasadSaranjit Singh

Abstract

A well-known problem of anti-tuberculosis fixed-dose combination (FDC) products containing rifampicin (R) and isoniazid (H) is the fall in bioavailability, in particular of R, when two or more drugs are present together. The same has been ascribed to hydrolysis of R to 3-formylrifamycin (3-RIF) under stomach acid conditions and reaction of the latter with H to form isonicotinyl hydrazone (HYD). The objective of present study was to explore whether the same reaction occurred when H was present along with rifapentine (Rp), a newer long acting rifamycin, which is structurally similar to R. Clinical trials are currently undergoing for co-administration of Rp with H in patients who had completed 2 months of standard chemotherapy. For the purpose, first a validated HPLC method was developed for the separation of Rp and H, and the same was used for the study of interaction between the two drugs. Like R, Rp was also found to convert to 3-RIF in acid conditions, which reacted further with H to form HYD. The pH-rate profile was also similar in shape to that established with the combination of R and H; maximum decomposition occurred at pH 2, where Rp loss was to an extent of approximately 30%, while corresponding decomposition of H was ap...Continue Reading

References

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Citations

Dec 17, 2008·Antimicrobial Agents and Chemotherapy·Jossy van den BoogaardRob E Aarnoutse
Mar 8, 2007·American Journal of Respiratory and Critical Care Medicine·Wing Wai Yew, Chi Chiu Leung
Jun 1, 2014·Journal of the Pediatric Infectious Diseases Society·Marc WeinerUNKNOWN Tuberculosis Trials Consortium PREVENT TB Pharmacokinetic Group
Sep 21, 2007·Journal of Pharmaceutical Sciences·Lisa Claire du ToitClement Penny
Mar 4, 2014·Journal of Pharmaceutical Sciences·John G Y ChanDaniela Traini
Jul 1, 2020·Drug Development and Industrial Pharmacy·Valentina PetruševskaAna Mornar
Dec 28, 2017·Carbohydrate Polymers·Christopher J WinslowAndrew P Neilson

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