| Study of the interaction between rifapentine and isoniazid under acid conditions. | |
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MedLine Citation:
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PMID: 16621412 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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 approximately 9%. These values were similar to those reported for the combination of R (approximately 33%) and H (approximately 10%). Hence, the study suggests that co-administration of Rp and H should be avoided, like in case of R and H, and the two drugs should not be formulated directly into a single dosage form. |
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Authors:
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Bhagwat Prasad; Hemant Bhutani; Saranjit Singh |
Publication Detail:
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Type: Journal Article Date: 2006-04-18 |
Journal Detail:
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Title: Journal of pharmaceutical and biomedical analysis Volume: 41 ISSN: 0731-7085 ISO Abbreviation: J Pharm Biomed Anal Publication Date: 2006 Jun |
Date Detail:
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Created Date: 2006-05-30 Completed Date: 2006-08-02 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8309336 Medline TA: J Pharm Biomed Anal Country: England |
Other Details:
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Languages: eng Pagination: 1438-41 Citation Subset: IM |
Affiliation:
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Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar 160062, Punjab, India. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antitubercular Agents
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chemistry* Chromatography, High Pressure Liquid / methods Drug Interactions Hydrogen-Ion Concentration Isoniazid / chemistry* Rifampin / analogs & derivatives*, chemistry |
| Chemical | |
Reg. No./Substance:
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0/Antitubercular Agents; 13292-46-1/Rifampin; 54-85-3/Isoniazid; 61379-65-5/rifapentine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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