Characterization of fimasartan metabolites in human liver microsomes and human plasma. (2nd January 2016)

• Record Type: Journal Article
• Authors: Lee, Ji-Yoon; Choi, Young Jae; Oh, Soo Jin; Chi, Yong Ha; Paik, Soo Heui; Lee, Ki Ho; Jung, Jae-Kyung; Ryu, Chang Seon; Kim, Kwon-Bok; Kim, Dong-Hyun; Yoon, Young-Ran; Kim, Sang Kyum
• Is Part Of: Xenobiotica. Volume 46:Number 1(2016:Jan.)
• Page Start: 40
• Page End: 51
• Publication Date: 2016-01-02
• Subjects: Fimasartan -- metabolic stability -- metabolite identification -- qualitative and quantitative analysis; Metabolism -- Periodicals; Drugs -- Physiological effect -- Periodicals; Food additives -- Periodicals; Chemicals -- Physiological effect -- Periodicals; Biochemistry -- Periodicals; Pharmaceutical Preparations -- metabolism -- Periodicals; Metabolism -- Periodicals; 574.133
• DOI: 10.3109/00498254.2015.1047429
• Languages: English
• ISSNs: 0049-8254

Abstract

Abstract: 1. The metabolites of fimasartan (FMS), a new angiotensin II receptor antagonist, were characterized in human liver microsomes (HLM) and human subjects. 2. We developed a method for a simultaneous quantitative and qualitative analysis using predictive multiple reaction monitoring information-dependent acquisition-enhanced product ion scanning. To characterize metabolic reactions, FMS metabolites were analyzed using quadrupole-time of flight mass spectrometer in full-scan mode. 3. The structures of metabolites were confirmed by comparison of chromatographic retention times and mass spectra with those of authentic metabolite standards. 4. In the cofactor-dependent microsomal metabolism study, the half-lives of FMS were 56.7, 247.9 and 53.3 min in the presence of NADPH, UDPGA and NADPH + UDPGA, respectively. 5. The main metabolic routes in HLM were S -oxidation, oxidative desulfuration, n -butyl hydroxylation and N -glucuronidation. 6. In humans orally administered with 120 mg FMS daily for 7 days, the prominent metabolites were FMS S -oxide and FMS N -glucuronide in the 0–8-h pooled plasma sample of each subject. 7. This study characterizes, for the first time, the metabolites of FMS in humans to provide information for its safe use in clinical medicine.