PMID- 27694226
OWN - NLM
STAT- MEDLINE
DCOM- 20180111
LR  - 20180324
IS  - 1521-009X (Electronic)
IS  - 0090-9556 (Linking)
VI  - 44
IP  - 12
DP  - 2016 Dec
TI  - Pharmacokinetics and Differential Regulation of Cytochrome P450 Enzymes in Type 1 
      Allergic Mice.
PG  - 1950-1957
AB  - Type 1 allergic diseases are characterized by elevated production of specific 
      immunoglobulin E (IgE) for each antigen and have become a significant health 
      problem worldwide. This study investigated the effect of IgE-mediated allergy on 
      drug pharmacokinetics. To further understand differential suppression of hepatic 
      cytochrome P450 (P450) activity, we examined the inhibitory effect of nitric 
      oxide (NO), a marker of allergic conditions. Seven days after primary 
      sensitization (PS7) or secondary sensitization (SS7), hepatic CYP1A2, CYP2C, 
      CYP2E1, and CYP3A activities were decreased to 45%-75% of the corresponding 
      control; however, CYP2D activity was not downregulated. PS7 and SS7 did not 
      change the expression levels of five P450 proteins. Disappearance of CYP1A2 and 
      CYP2D substrates from the plasma was not significantly different between allergic 
      mice and control mice. In contrast, the area under the curve of a CYP1A2-mediated 
      metabolite in PS7 and SS7 mice was reduced by 50% of control values. Total 
      clearances of a CYP2E1 substrate in PS7 and SS7 mice were significantly decreased 
      to 70% and 50% respectively, of the control without altering plasma protein 
      binding. Hepatic amounts of CYP1A2 and CYP2E1 substrates were enhanced by 
      allergic induction, being responsible for each downregulated activity. NO 
      scavenger treatment completely improved the downregulated P450 activities. 
      Therefore, our data suggest that the onset of IgE-mediated allergy alters the 
      pharmacokinetics of major P450-metabolic capacity-limited drugs except for CYP2D 
      drugs. NO is highly expected to participate in regulatory mechanisms of the four 
      P450 isoforms.
CI  - Copyright (c) 2016 by The American Society for Pharmacology and Experimental 
      Therapeutics.
FAU - Tanino, Tadatoshi
AU  - Tanino T
AD  - Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan.
FAU - Komada, Akira
AU  - Komada A
AD  - Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan.
FAU - Ueda, Koji
AU  - Ueda K
AD  - Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan.
FAU - Bando, Toru
AU  - Bando T
AD  - Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan.
FAU - Nojiri, Yukie
AU  - Nojiri Y
AD  - Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan.
FAU - Ueda, Yukari
AU  - Ueda Y
AD  - Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan.
FAU - Sakurai, Eiichi
AU  - Sakurai E
AD  - Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan 
      esakurai@ph.bunri-u.ac.jp.
LA  - eng
PT  - Journal Article
DEP - 20160930
PL  - United States
TA  - Drug Metab Dispos
JT  - Drug metabolism and disposition: the biological fate of chemicals
JID - 9421550
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
SB  - IM
MH  - Animals
MH  - Cytochrome P-450 Enzyme System/*metabolism
MH  - Down-Regulation/physiology
MH  - Female
MH  - Hypersensitivity/*metabolism
MH  - Immunoglobulin E/metabolism
MH  - Liver/metabolism
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Nitric Oxide/metabolism
EDAT- 2016/10/04 06:00
MHDA- 2018/01/13 06:00
CRDT- 2016/10/04 06:00
PHST- 2016/07/11 00:00 [received]
PHST- 2016/09/28 00:00 [accepted]
PHST- 2016/10/04 06:00 [pubmed]
PHST- 2018/01/13 06:00 [medline]
PHST- 2016/10/04 06:00 [entrez]
AID - dmd.116.072462 [pii]
AID - 10.1124/dmd.116.072462 [doi]
PST - ppublish
SO  - Drug Metab Dispos. 2016 Dec;44(12):1950-1957. doi: 10.1124/dmd.116.072462. Epub 
      2016 Sep 30.