Human pregnane X receptor (hPXR) gene polymorphisms (spanning exon 2 to exon 5) and alternative mRNA splicing were investigated as possible contributors to individual variability in CYP3A metabolic activity measured both in vivo and in vitro. None of the 9 variants evaluated, including the 2 most common nonsynonymous variants (Pro27Ser and Gly36Arg), was found to be associated with midazolam 1'-hydroxylation rate measured in a bank of human livers (48 European Americans, 4 African Americans, 2 Hispanics). In contrast, 3 linked hPXR variants (g.252A > G, g.275A > G, and g.4760G > A) were significantly (P < .05) associated with oral midazolam clearance in a mixed race/ethnicity population (n = 26) and the African American subpopulation (n = 14) but not in European Americans (n = 9). Although the amount of hPXR mRNA normally spliced at the exon 4-5 junction correlated well with midazolam 1'-hydroxylation activities (P < .05), none of the 6 hPXR mRNA splice variants identified was associated with midazolam 1'-hydroxylation. In conclusion, several hPXR polymorphisms have been identified that may have predictive value for oral midazolam clearance, particularly in African Americans.
Pharmacology, Toxicology and Pharmaceutical Science
2
11%
Computer Science
1
6%
Energy
1
6%
Medicine and Dentistry
1
6%
Other
0
0%
Unknown
5
28%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 09 July 2022.
All research outputs
#8,534,976
of 25,373,627 outputs
Outputs from The Journal of Clinical Pharmacology
#803
of 2,418 outputs
Outputs of similar age
#71,449
of 208,503 outputs
Outputs of similar age from The Journal of Clinical Pharmacology
#417
of 1,321 outputs
Altmetric has tracked 25,373,627 research outputs across all sources so far. This one is in the 43rd percentile – i.e., 43% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,418 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.8. This one is in the 30th percentile – i.e., 30% of its peers scored the same or lower than it.
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We're also able to compare this research output to 1,321 others from the same source and published within six weeks on either side of this one. This one is in the 10th percentile – i.e., 10% of its contemporaries scored the same or lower than it.
