ELIZA cgi-bash version rev. 1.91
- Medical English LInking keywords finder for the PubMed Zipped Archive (ELIZA) -

return kwic search for higher out of >500 occurrences
487192 occurrences (No.29 in the rank) during 5 years in the PubMed. [cache]
199) In vitro metabolism experiments revealed that the relative contribution of oxidation and glucuronidation was concentration-dependent, with glucuronidation as the predominant pathway at higher concentrations and the oxidative process becoming more important at lower concentrations near clinical exposure range.
--- ABSTRACT ---
PMID:33952610 DOI:10.1124/dmd.120.000349
2021 Drug metabolism and disposition: the biological fate of chemicals
* Evaluation of the Absorption, Metabolism, and Excretion of a Single Oral 1-mg Dose of Tropifexor in Healthy Male Subjects and the Concentration Dependence of Tropifexor Metabolism.
- Tropifexor (NVP-LJN452) is a highly potent, selective, nonsteroidal, non-bile acid farnesoid X receptor agonist for the treatment of nonalcoholic steatohepatitis. Its absorption, metabolism, and excretion were studied after a 1-mg oral dose of [14C]tropifexor was given to four healthy male subjects. Mass balance was achieved with ∼94% of the administered dose recovered in excreta through a 312-hour collection period. Fecal excretion of tropifexor-related radioactivity played a major role (∼65% of the total dose). Tropifexor reached a maximum blood concentration (Cmax) of 33.5 ng/ml with a median time to reach Cmax of 4 hours and was eliminated with a plasma elimination half-life of 13.5 hours. Unchanged tropifexor was the principal drug-related component found in plasma (∼92% of total radioactivity). Two minor oxidative metabolites, M11.6 and M22.4, were observed in circulation. Tropifexor was eliminated predominantly via metabolism with >68% of the dose recovered as metabolites in excreta. Oxidative metabolism appeared to be the major clearance pathway of tropifexor. Metabolites containing multiple oxidative modifications and combined oxidation and glucuronidation were also observed in human excreta. The involvement of direct glucuronidation could not be ruled out based on previous in vitro and nonclinical in vivo studies indicating its contribution to tropifexor clearance. The relative contribution of the oxidation and glucuronidation pathways appeared to be dose-dependent upon further in vitro investigation. Because of these complexities and the instability of glucuronide metabolites in the gastrointestinal tract, the contribution of glucuronidation remained undefined in this study. SIGNIFICANCE STATEMENT: Tropifexor was found to be primarily cleared from the human body via oxidative metabolism. In vitro metabolism experiments revealed that the relative contribution of oxidation and glucuronidation was concentration-dependent, with glucuronidation as the predominant pathway at higher concentrations and the oxidative process becoming more important at lower concentrations near clinical exposure range. The body of work demonstrated the importance of carefully designed in vivo and in vitro experiments for better understanding of disposition processes during drug development.
--- ABSTRACT END ---
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(1)37 than (14)5 mortality (27)2 activation (40)2 or
(2)33 in (15)4 concentrations (28)2 anti-E (41)2 percentage
(3)28 levels (16)4 proportion (29)2 at (42)2 performing
(4)27 risk (17)4 rate (30)2 auditory-perceptual (43)2 potency
(5)11 rates (18)4 regions (31)2 cognitive (44)2 risk,
(6)10 among (19)3 consumption (32)2 compared (45)2 scores
(7)8 for (20)3 frequency (33)2 disease (46)2 selectivity
(8)8 prevalence (21)3 plasma (34)2 doses (47)2 social
(9)7 education (22)3 quality (35)2 endostatin (48)2 stimulation
(10)7 level (23)3 sensitivity (36)2 extent (49)2 to
(11)6 expression (24)3 strength (37)2 from (50)2 tumor
(12)5 and (25)2 F (38)2 glutamate-cysteine (51)2 weight
(13)5 incidence (26)2 NAFLD (39)2 odds

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--- WordNet output for higher --- =>幹部, おえら方 Overview of adj higher The adj higher has 2 senses (first 2 from tagged texts) 1. (10) higher -- (advanced in complexity or elaboration; "higher finance"; "higher mathematics") 2. (1) higher -- (of education beyond the secondary level; "higher education"; "higher learning") Overview of adj high The adj high has 7 senses (first 5 from tagged texts) 1. (134) high -- (greater than normal in degree or intensity or amount; "a high temperature"; "a high price"; "the high point of his career"; "high risks"; "has high hopes"; "the river is high"; "he has a high opinion of himself") 2. (51) high -- ((literal meaning) being at or having a relatively great or specific elevation or upward extension (sometimes used in combinations like `knee-high'); "a high mountain"; "high ceilings"; "high buildings"; "a high forehead"; "a high incline"; "a foot high") 3. (10) eminent, high -- (standing above others in quality or position; "people in high places"; "the high priest"; "eminent members of the community") 4. (7) high, high-pitched -- (used of sounds and voices; high in pitch or frequency) 5. (2) high, in high spirits -- (happy and excited and energetic) 6. gamey, gamy, high -- ((used of the smell of meat) smelling spoiled or tainted) 7. high, mellow -- (slightly and pleasantly intoxicated from alcohol or a drug (especially marijuana)) --- WordNet end ---