PMID- 28523515
OWN - NLM
STAT- MEDLINE
DCOM- 20180518
LR  - 20220330
IS  - 1550-7416 (Electronic)
IS  - 1550-7416 (Linking)
VI  - 19
IP  - 4
DP  - 2017 Jul
TI  - Distribution of Exogenous and Endogenous CYP3A Markers and Related Factors in 
      Healthy Males and Females.
PG  - 1196-1204
LID - 10.1208/s12248-017-0090-8 [doi]
AB  - Cytochrome P450 (CYP) 3A is an important drug-metabolizing enzyme in humans. 
      Assessing CYP3A activity is necessary for predicting therapeutic outcomes or the 
      potential adverse events of various therapeutics. This study sought to evaluate 
      the distribution of endogenous and exogenous markers reflecting hepatic CYP3A 
      activity and related factors affecting its activity in healthy male and female. 
      Each subject was given a single 1 mg dose of midazolam intravenously. 
      Pharmacokinetics, pharmacometabolomics, and pharmacogenomics analyses were 
      performed to evaluate CYP3A activity. Urinary and plasma steroids were quantified 
      with gas chromatography coupled with triple-quadrupole mass spectrometry (GC-MS), 
      and the concentrations of midazolam and its metabolites were quantified with 
      liquid chromatography coupled with electrospray tandem mass spectrometry 
      (LC-MS/MS). A total of 100 subjects completed this study. Midazolam clearance 
      (MDZ CL) and the metabolic ratio (MDZ MR) were significantly correlated with 
      6beta-OH-cortisol/cortisol and 6beta-OH-cortisone/cortisone. MDZ CL, 
      6beta-OH-cortisol/cortisol, and 6beta-OH-cortisone/cortisone decreased with increasing 
      age (Pearson r = -0.333, -0.329, and -0.528, respectively; P < 0.05). When the 
      markers were compared according to sex, MDZ CL and 6beta-OH-cortisol/cortisol showed 
      significant difference between sexes. However, MDZ CL was higher in female group 
      than male group and 6beta-OH-cortisol/cortisol was higher in male group than female 
      group. No significant differences in markers were found when comparing 
      progesterone levels. Our results indicate that both exogenous and endogenous 
      markers showed decreased CYP3A activity with increasing age, which suggested that 
      age could be a factor that significantly influences CYP3A activity.
FAU - Lee, Jieon
AU  - Lee J
AD  - Department of Clinical Pharmacology and Therapeutics, Seoul National University 
      College of Medicine and Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-799, 
      Republic of Korea.
FAU - Kim, Andrew HyoungJin
AU  - Kim AH
AD  - Department of Clinical Pharmacology and Therapeutics, Seoul National University 
      College of Medicine and Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-799, 
      Republic of Korea.
FAU - Yi, SoJeong
AU  - Yi S
AD  - Department of Clinical Pharmacology and Therapeutics, Seoul National University 
      College of Medicine and Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-799, 
      Republic of Korea.
FAU - Lee, SeungHwan
AU  - Lee S
AD  - Department of Clinical Pharmacology and Therapeutics, Seoul National University 
      College of Medicine and Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-799, 
      Republic of Korea.
FAU - Yoon, Seo Hyun
AU  - Yoon SH
AD  - Department of Clinical Pharmacology and Therapeutics, Seoul National University 
      College of Medicine and Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-799, 
      Republic of Korea.
FAU - Yu, Kyung-Sang
AU  - Yu KS
AD  - Department of Clinical Pharmacology and Therapeutics, Seoul National University 
      College of Medicine and Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-799, 
      Republic of Korea.
FAU - Jang, In-Jin
AU  - Jang IJ
AD  - Department of Clinical Pharmacology and Therapeutics, Seoul National University 
      College of Medicine and Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-799, 
      Republic of Korea.
FAU - Cho, Joo-Youn
AU  - Cho JY
AD  - Department of Clinical Pharmacology and Therapeutics, Seoul National University 
      College of Medicine and Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-799, 
      Republic of Korea. joocho@snu.ac.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170518
PL  - United States
TA  - AAPS J
JT  - The AAPS journal
JID - 101223209
RN  - 0 (Biomarkers)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP3A)
RN  - R60L0SM5BC (Midazolam)
SB  - IM
MH  - Adult
MH  - Biomarkers/blood
MH  - Chromatography, Gas/methods
MH  - Chromatography, Liquid/methods
MH  - Cytochrome P-450 CYP3A/*metabolism
MH  - Female
MH  - Healthy Volunteers
MH  - Humans
MH  - Male
MH  - Mass Spectrometry/methods
MH  - Midazolam/pharmacokinetics
MH  - Middle Aged
MH  - Young Adult
OTO - NOTNLM
OT  - CYP3A
OT  - biomarkers
OT  - endogenous metabolites
OT  - midazolam
OT  - pharmacometabolomics
EDAT- 2017/05/20 06:00
MHDA- 2018/05/19 06:00
CRDT- 2017/05/20 06:00
PHST- 2016/12/06 00:00 [received]
PHST- 2017/04/17 00:00 [accepted]
PHST- 2017/05/20 06:00 [pubmed]
PHST- 2018/05/19 06:00 [medline]
PHST- 2017/05/20 06:00 [entrez]
AID - 10.1208/s12248-017-0090-8 [pii]
AID - 10.1208/s12248-017-0090-8 [doi]
PST - ppublish
SO  - AAPS J. 2017 Jul;19(4):1196-1204. doi: 10.1208/s12248-017-0090-8. Epub 2017 May 
      18.