In Vitro Competitive Metabolism Study of Olmesartan Medoxomil in Rat Liver S9 Fractions Using LC/MS
نویسندگان
چکیده
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.
منابع مشابه
Hepatic, intestinal, renal, and plasma hydrolysis of prodrugs in human, cynomolgus monkey, dog, and rat: implications for in vitro-in vivo extrapolation of clearance of prodrugs.
Hydrolysis plays an important role in metabolic activation of prodrugs. In the current study, species and in vitro system differences in hepatic and extrahepatic hydrolysis were investigated for 11 prodrugs. Ten prodrugs in the data set are predominantly hydrolyzed by carboxylesterases (CES), whereas olmesartan medoxomil is also metabolized by carboxymethylenebutenolidase (CMBL) and paraoxonase...
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242 words Introduction: 491 words Discussion: 1168 words Abbreviations: ARB, angiotensin receptor blocker; AM, azilsartan medoxomil; BNPP, bis-p-nitrophenylphosphate; CC, candesartan cilexetil; CES, carboxylesterase; CMBL, carboxymethylenebutenolidase homolog; Km, Michaelis constant; LC-MS/MS, liquid chromatography with tandem mass spectrometry; OM, olmesartan medoxomil; S9, This article has no...
متن کاملDmd057372 1522..1531
Hydrolysis plays an important role in metabolic activation of prodrugs. In the current study, species and in vitro system differences in hepatic and extrahepatic hydrolysis were investigated for 11 prodrugs. Ten prodrugs in the data set are predominantly hydrolyzed by carboxylesterases (CES), whereas olmesartan medoxomil is also metabolized by carboxymethylenebutenolidase (CMBL) and paraoxonase...
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