In Vitro Competitive Metabolism Study of Olmesartan Medoxomil in Rat Liver S9 Fractions Using LC/MS
M. Gandhimathi, Rahul Baghla, S. Subramanian, T.K Ravi
DOI: 10.4236/pp.2011.24048   PDF    HTML     6,044 Downloads   12,244 Views   Citations

Abstract

Olmesartan Medoxomil (OLM), Ramipril (RPL) & Fenofibric acid (FA) are used to treat hypertension and cardiovascular disease. These drugs undergo hydrolytic metabolism by the enzyme liver esterase and converts into their respective active metabolites Olmesartan (OL), Ramiprilat (RPT) and Fenofibric acid (FA) for OLM, RPL and FEN respectively. In this study the competitive metabolism of OLM, in presence of RPL and FEN was investigated in rat liver s9 fractions using a validated LC-MS method. Olmesartan Medoxomil was found to be highly reactive to the rat liver S9 fractions and formation of active metabolite Olmesartan is highest. The rate of formation of active metabolite Olmesartan reduced by 12.68% in the presence Ramipril and 6.56% in presence of Fenofibrate. A marked reduction of 18.96% was found in the formation of active metabolite Olmesartan from Olmesartan Medoxomil when all the three drugs are in combination.

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Gandhimathi, M. , Baghla, R. , Subramanian, S. and Ravi, T. (2011) In Vitro Competitive Metabolism Study of Olmesartan Medoxomil in Rat Liver S9 Fractions Using LC/MS. Pharmacology & Pharmacy, 2, 370-374. doi: 10.4236/pp.2011.24048.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] N.Sultana, M.S. Arayane, S.S Ali and S. Sajid, “Simultaneous determination of olmesartan medoxomil and irbesartan and hydrochlorothiazide in pharmaceutical formulations and human serum using high performance liquid chromatography” Chinese Journal of Chromatography, Vol. 26, No. 5, 2008, pp. 544-549.
[2] B. Lisiane, R. C. Rochele, D. L. Carolina B. M. Ana and F.E. Pedro, “Stability-Indicating LC Determination of a New Antihypertensive, Olmesartan Medoxomil in Tablets” Chromatographia, Vol. 68, 2008, pp. 991-996.
[3] P. D. Bari and A. Rote, “RP-LC and HPTLC Methods for the Determination of Olmesartan Medoxomil and Hydrochlorothiazide in Combined Tablet Dosage Forms,” Chromatographia, Vol. 69, 2009, pp. 1469-1472.
[4] Chrysant and G. Steven, “Amlodipine besylate/olmesar- tan medoximil fixed combination for the treatment of hypertension,” Expert Review of Cardiovascular Therapy, Vol. 7, No. 8, 2009, pp. 887-895.
[5] D. Liua, P. Hu, N. Matsushima, X. Lia, L. Lia and Ji, “Quantitative determination of olmesartan in human plasma and urine by liquid chromatography coupled to tandem mass spectrometry”, Journal of Chromatography B, Vol. 856, No.1-2, 2007, pp. 190-197.
[6] B. Yuan, X. Wang, F. Zhang, J. Jia and F. Tang, “Simultaneous Determination of Ramipril and Its Active Metabolite Ramiprilat in Human Plasma by LC–MS–MS,” Chromatographia, Vol. 68, No. 7-8, pp. 533-539.
[7] Persson and B. Arne, “Interference from a glucuronide metabolite in the determination of ramipril and ramiprilat in human plasma and urine by gas chromatography–mass spectrometry,” Journal of Pharmaceutical and Biomedical Analysis, Vol. 40, No.3, 2006, pp.794-797.
[8] L Xiao-yang, “High-performance liquid chromatography?mass spectrometric analysis of ramipril and its active metabolite ramiprilat in human serum: Application to a pharmacokinetic study in the Chinese volunteers,” Journal of Pharmaceutical and Biomedical Analysis, Vol. 40, No. 2, 2006, pp. 478-483.
[9] Z. Zhimeng, “Liquid chromatography-mass spectrometry method for determination of ramipril and its active metabolite ramiprilat in human plasma,” Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, Vol. 779, No. 2, 2002, pp. 297-306.
[10] G. E. Linda, “Evaluation of the potential for pharmacokinetic interaction between fenofibrate and ezetimibe: A phase I, open-label, multiple-dose, three-period crossover study in healthy subjects,” Clinical Therapeutics, Vol. 28, No. 3, 2006, pp.373.
[11] Z. Zhu, A. Vachareau and L. Neirinck, “Liquid chromatography–mass spectrometry method for determination of ramipril and its active metabolite ramiprilat in human plasma” Journal of Chromatography B, Vol. 779, No. 2, 2002, pp. 297-306.
[12] V. P. Chintan, P.K Amit, D.C. Anandi and T.P Kalpesh, “Validated Absorption Factor Spectrophotometric and Reversed-Phase High-Performance Liquid Chromatographic Methods for the Determination of Ramipril and Olmesartan Medoxomil in Pharmaceutical Formulations,” Eurasian Journal of Analytical Chemistry, Vol. 2, No. 3, 2007, pp. 159-171.

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