PMID- 31002385
OWN - NLM
STAT- MEDLINE
DCOM- 20200513
LR  - 20200513
IS  - 1532-6535 (Electronic)
IS  - 0009-9236 (Linking)
VI  - 106
IP  - 4
DP  - 2019 Oct
TI  - Use of 4beta-Hydroxycholesterol Plasma Concentrations as an Endogenous Biomarker of 
      CYP3A Activity: Clinical Validation in Individuals With Type 2 Diabetes.
PG  - 831-840
LID - 10.1002/cpt.1472 [doi]
AB  - The relevance of endogenous 4beta-hydroxycholesterol (4beta-OHC) plasma concentrations 
      or of the 4beta-OHC/total cholesterol concentration ratio (4beta-OHC ratio) as 
      surrogate markers of cytochrome P450 3A (CYP3A) activity was evaluated in 
      individuals with (n = 38) or without (n = 35) type 2 diabetes (T2D). Midazolam 
      was used as a comparator to validate exploratory measures of phenotypic CYP3A 
      activity. Metabolic ratios of orally administered midazolam in nondiabetic and 
      diabetic populations correlated significantly with 4beta-OHC (r(s)  = 0.64 and 0.48; 
      P </= 0.003) and 4beta-OHC ratio (r(s)  = 0.69 and 0.46; P </= 0.003), respectively. 
      Activity of CYP3A was lower in the T2D population compared with nondiabetic 
      subjects; this decrease was reflected in 4beta-OHC concentrations (24.33 vs. 
      12.58 ng/mL; P < 0.0001) and 4beta-OHC ratio (0.13 vs. 0.09 (x 10(4) ); P < 0.0002). 
      These results suggest that 4beta-OHC should be considered as a valid, convenient, 
      and easy to use endogenous biomarker of CYP3A activity in patients.
CI  - (c) 2019 The Authors Clinical Pharmacology & Therapeutics (c) 2019 American Society 
      for Clinical Pharmacology and Therapeutics.
FAU - Gravel, Sophie
AU  - Gravel S
AD  - Faculty of Pharmacy, Universite de Montreal, Montreal, Quebec, Canada.
AD  - CRCHUM-Centre de Recherche du Centre Hospitalier de l'Universite de Montreal, 
      Montreal, Quebec, Canada.
FAU - Chiasson, Jean-Louis
AU  - Chiasson JL
AD  - CRCHUM-Centre de Recherche du Centre Hospitalier de l'Universite de Montreal, 
      Montreal, Quebec, Canada.
AD  - CHUM, Centre Hospitalier de l'Universite de Montreal, Montreal, Quebec, Canada.
AD  - Faculty of Medicine, Universite of Montreal, Montreal, Quebec, Canada.
FAU - Gaudette, Fleur
AU  - Gaudette F
AD  - CRCHUM-Centre de Recherche du Centre Hospitalier de l'Universite de Montreal, 
      Montreal, Quebec, Canada.
FAU - Turgeon, Jacques
AU  - Turgeon J
AD  - Faculty of Pharmacy, Universite de Montreal, Montreal, Quebec, Canada.
AD  - CRCHUM-Centre de Recherche du Centre Hospitalier de l'Universite de Montreal, 
      Montreal, Quebec, Canada.
FAU - Michaud, Veronique
AU  - Michaud V
AD  - Faculty of Pharmacy, Universite de Montreal, Montreal, Quebec, Canada.
AD  - CRCHUM-Centre de Recherche du Centre Hospitalier de l'Universite de Montreal, 
      Montreal, Quebec, Canada.
LA  - eng
GR  - 299309/CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190605
PL  - United States
TA  - Clin Pharmacol Ther
JT  - Clinical pharmacology and therapeutics
JID - 0372741
RN  - 0 (Biomarkers)
RN  - 0 (Hydroxycholesterols)
RN  - 0 (Hypnotics and Sedatives)
RN  - 17320-10-4 (cholest-5-ene-3,4-diol)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP3A)
RN  - R60L0SM5BC (Midazolam)
SB  - IM
MH  - Biological Variation, Population
MH  - Biomarkers/blood
MH  - Cholesterol/blood
MH  - Cytochrome P-450 CYP3A/*metabolism
MH  - *Diabetes Mellitus, Type 2/blood/drug therapy/enzymology
MH  - Endophenotypes
MH  - Female
MH  - Humans
MH  - Hydroxycholesterols/*blood
MH  - Hypnotics and Sedatives/pharmacokinetics
MH  - Male
MH  - Metabolic Clearance Rate
MH  - Midazolam/*pharmacokinetics
MH  - Middle Aged
MH  - Reproducibility of Results
EDAT- 2019/04/20 06:00
MHDA- 2020/05/14 06:00
CRDT- 2019/04/20 06:00
PHST- 2019/02/06 00:00 [received]
PHST- 2019/03/29 00:00 [accepted]
PHST- 2019/04/20 06:00 [pubmed]
PHST- 2020/05/14 06:00 [medline]
PHST- 2019/04/20 06:00 [entrez]
AID - 10.1002/cpt.1472 [doi]
PST - ppublish
SO  - Clin Pharmacol Ther. 2019 Oct;106(4):831-840. doi: 10.1002/cpt.1472. Epub 2019 
      Jun 5.