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

return kwic search for further out of >500 occurrences
298283 occurrences (No.79 in the rank) during 5 years in the PubMed. [cache]
136) This finding may be important to consider when administering narrow-therapeutic-index medications metabolized by CYP2C9 and also compels further investigation to characterize novel genetic variation in understudied populations.
--- ABSTRACT ---
PMID:33632714 DOI:10.1124/dmd.120.000301
2021 Drug metabolism and disposition: the biological fate of chemicals
* In Vivo Functional Effects of CYP2C9 M1L, a Novel and Common Variant in the Yup'ik Alaska Native Population.
- Alaska Native people are under-represented in genetic research but have unique gene variation that may critically impact their response to pharmacotherapy. Full resequencing of CYP2C9 in a cross-section of this population identified CYP2C9 Met1Leu (M1L), a novel, relatively common single nucleotide polymorphism hypothesized to confer CYP2C9 poor metabolizer phenotype by disrupting the start codon. M1L is present at a minor allele frequency of 6.3% in Yup'ik Alaska Native people and thus can contribute to the risk of an adverse drug response from narrow-therapeutic-index CYP2C9 substrates such as (S)-warfarin. This study's objective was to characterize the catalytic efficiency of the Leu1 variant enzyme in vivo by evaluating the pharmacokinetic behavior of naproxen, a probe substrate for CYP2C9 activity, in genotyped Yup'ik participants. We first confirmed the selectivity of (S)-naproxen O-demethylation by CYP2C9 using activity-phenotyped human liver microsomes and selective cytochrome P450 inhibitors and then developed and validated a novel liquid chromatography mass spectrometry method for simultaneous quantification of (S)-naproxen, (S)-O-desmethylnaproxen, and naproxen acyl glucuronide in human urine. The average ratio of (S)-O-desmethylnaproxen to unchanged (S)-naproxen in urine was 18.0 ± 8.0 (n = 11) for the homozygous CYP2C9Met1 reference group and 10.3 ± 6.6 (n = 11) for the Leu1 variant carrier group (P = 0.011). The effect of M1L variation on CYP2C9 function and its potential to alter the pharmacokinetics of drugs metabolized by the enzyme has clinical implications and should be included in a variant screening panel when pharmacogenetic testing in the Alaska Native population is warranted. SIGNIFICANCE STATEMENT: The novel CYP2C9 Met1Leu variant in Alaska Native people was recently identified. This study validated (S)-naproxen as a CYP2C9 probe substrate to characterize the in vivo functional activity of the CYP2C9 Leu1 variant. The results of this pharmacogenetic-pharmacokinetic study suggest that the CYP2C9 Leu1 variant exhibits loss of enzyme activity. This finding may be important to consider when administering narrow-therapeutic-index medications metabolized by CYP2C9 and also compels further investigation to characterize novel genetic variation in understudied populations.
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[frequency of next (right) word to further]
(1)83 research (16)4 validation (31)2 and (46)2 high-quality
(2)43 studies (17)3 confirmed (32)2 attention (47)2 inform
(3)22 investigation (18)3 demonstrate (33)2 characterization (48)2 insight
(4)9 analysis (19)3 demonstrated (34)2 clinical (49)2 reduce
(5)9 study (20)3 highlight (35)2 considerations (50)2 research,
(6)7 the (21)3 identify (36)2 develop (51)2 revealed
(7)7 work (22)3 in (37)2 developing (52)2 screening
(8)5 development (23)3 investigated (38)2 discussion (53)2 showed
(9)5 evidence (24)3 investigations (39)2 divided (54)2 structure-based
(10)4 evaluate (25)3 literature (40)2 enhanced (55)2 studied
(11)4 evaluation (26)3 our (41)2 evaluated (56)2 supported
(12)4 exploration (27)3 show (42)2 evaluations (57)2 tested
(13)4 explore (28)3 we (43)2 examined (58)2 this
(14)4 improve (29)2 aid (44)2 explored (59)2 understand
(15)4 investigate (30)2 analyses (45)2 extend (60)2 understanding

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--- WordNet output for further --- =>1.さらにずっと, さらに先に, 一層遠く, その上, 更に, もっと遠い, なお一層の, さらに遠く, もっと先に, いっそうはるかに, さらにまた, さらになお(furthermore), 2.進める, 助成する, 促進する Overview of verb further The verb further has 2 senses (first 2 from tagged texts) 1. (7) foster, further -- (promote the growth of; "Foster our children's well-being and education") 2. (2) promote, advance, boost, further, encourage -- (contribute to the progress or growth of; "I am promoting the use of computers in the classroom") Overview of adj further The adj further has 1 sense (first 1 from tagged texts) 1. (2) further, farther -- (more distant in especially degree; "nothing could be further from the truth"; "further from our expectations"; "farther from the truth"; "farther from our expectations") Overview of adv further The adv further has 3 senses (first 3 from tagged texts) 1. (33) further, farther -- (to or at a greater extent or degree or a more advanced stage (`further' is used more often than `farther' in this abstract sense); "further complicated by uncertainty about the future"; "let's not discuss it further"; "nothing could be further from the truth"; "they are further along in their research than we expected"; "the application of the law was extended farther"; "he is going no farther in his studies") 2. (10) further -- (in addition or furthermore; "if we further suppose"; "stated further that he would not cooperate with them"; "they are definitely coming; further, they should be here already") 3. (1) farther, further -- (to or at a greater distance in time or space (`farther' is used more frequently than `further' in this physical sense); "farther north"; "moved farther away"; "farther down the corridor"; "the practice may go back still farther to the Druids"; "went only three miles further"; "further in the future") Overview of adv far The adv far has 5 senses (first 4 from tagged texts) 1. (61) far -- (to a considerable degree; very much; "a far far better thing that I do"; "felt far worse than yesterday"; "eyes far too close together") 2. (39) far -- (at or to or from a great distance in space; "he traveled far"; "strayed far from home"; "sat far away from each other") 3. (22) far -- (at or to a certain point or degree; "I can only go so far before I have to give up"; "how far can we get with this kind of argument?") 4. (3) far -- (remote in time; "if we could see far into the future"; "all that happened far in the past") 5. far -- (to an advanced stage or point; "a young man who will go very far") --- WordNet end ---