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

return kwic search for human out of >500 occurrences
482327 occurrences (No.32 in the rank) during 5 years in the PubMed. [cache]
64) Translational and ADME Sciences Leadership Group Induction Working Group (IWG) presents an analysis on the time course for cytochrome P450 induction in primary human hepatocytes.
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PMID:33139460 DOI:10.1124/dmd.120.000055
2021 Drug metabolism and disposition: the biological fate of chemicals
* Considerations from the Innovation and Quality Induction Working Group in Response to Drug-Drug Interaction Guidance from Regulatory Agencies: Guidelines on Model Fitting and Recommendations on Time Course for In Vitro Cytochrome P450 Induction Studies Including Impact on Drug Interaction Risk Assessment.
- Translational and ADME Sciences Leadership Group Induction Working Group (IWG) presents an analysis on the time course for cytochrome P450 induction in primary human hepatocytes. Induction of CYP1A2, CYP2B6, and CYP3A4 was evaluated by seven IWG laboratories after incubation with prototypical inducers (omeprazole, phenobarbital, rifampicin, or efavirenz) for 6-72 hours. The effect of incubation duration and model-fitting approaches on induction parameters (Emax and EC50) and drug-drug interaction (DDI) risk assessment was determined. Despite variability in induction response across hepatocyte donors, the following recommendations are proposed: 1) 48 hours should be the primary time point for in vitro assessment of induction based on mRNA level or activity, with no further benefit from 72 hours; 2) when using mRNA, 24-hour incubations provide reliable assessment of induction and DDI risk; 3) if validated using prototypical inducers (>10-fold induction), 12-hour incubations may provide an estimate of induction potential, including characterization as negative if <2-fold induction of mRNA and no concentration dependence; 4) atypical dose-response ("bell-shaped") curves can be addressed by removing points outside an established confidence interval and %CV; 5) when maximum fold induction is well defined, the choice of nonlinear regression model has limited impact on estimated induction parameters; 6) when the maximum fold induction is not well defined, conservative DDI risk assessment can be obtained using sigmoidal three-parameter fit or constraining logistic three- or four-parameter fits to the maximum observed fold induction; 7) preliminary data suggest initial slope of the fold induction curve can be used to estimate Emax/EC50 and for induction risk assessment. SIGNIFICANCE STATEMENT: Regulatory agencies provide inconsistent guidance on the optimum length of time to evaluate cytochrome P450 induction in human hepatocytes, with EMA recommending 72 hours and FDA suggesting 48-72 hours. The Induction Working Group analyzed a large data set generated by seven member companies and determined that induction response and drug-drug risk assessment determined after 48-hour incubations were representative of 72-hour incubations. Additional recommendations are provided on model-fitting techniques for induction parameter estimation and addressing atypical concentration-response curves.
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[frequency of next (right) word to human]
(1)29 health (21)4 laboratory (41)2 MC (61)2 leukocyte
(2)25 and (22)4 liver (42)2 PSCs (62)2 lifespan
(3)10 hepatocytes (23)4 serum (43)2 RNA (63)2 may
(4)9 brain (24)3 beings (44)2 activities (64)2 medicine
(5)9 gut (25)3 health, (45)2 adipocytes (65)2 microbiome
(6)8 studies (26)3 hepatocyte (46)2 behavior (66)2 movement,
(7)7 milk (27)3 infection (47)2 behaviour (67)2 nervous
(8)6 exposure (28)3 jejunum (48)2 blood (68)2 or
(9)6 immunodeficiency (29)3 livers (49)2 cell (69)2 participants,
(10)6 skin (30)3 lung (50)2 cerebral (70)2 pathogen
(11)5 body (31)3 macrophages (51)2 colonoids (71)2 populations,
(12)5 clinical (32)3 oral (52)2 data (72)2 primate
(13)5 disease (33)3 participants (53)2 diseases, (73)2 ratings
(14)5 diseases (34)3 plasma (54)2 genome (74)2 research
(15)5 interaction (35)3 seasonal (55)2 genomic (75)2 resources,
(16)5 papillomavirus (36)2 ALDH1A3 (56)2 hepatocytes, (76)2 studies,
(17)5 subjects (37)2 AV (57)2 hepatoma (77)2 trials
(18)4 breast (38)2 Biomonitoring (58)2 immune (78)2 umbilical
(19)4 bronchial (39)2 CRC (59)2 induced
(20)4 intestinal (40)2 Genome (60)2 interactions

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--- WordNet output for human --- =>人間らしい, 人間の, 人, 人間 Overview of noun human The noun human has 1 sense (first 1 from tagged texts) 1. (5) homo, man, human being, human -- (any living or extinct member of the family Hominidae characterized by superior intelligence, articulate speech, and erect carriage) Overview of adj human The adj human has 3 senses (first 3 from tagged texts) 1. (46) human -- (characteristic of humanity; "human nature") 2. (19) human -- (relating to a person; "the experiment was conducted on 6 monkeys and 2 human subjects") 3. (15) human -- (having human form or attributes as opposed to those of animals or divine beings; "human beings"; "the human body"; "human kindness"; "human frailty") --- WordNet end ---