summary of information on human cyp enzymes: … · summary of information on human cyp enzymes:...
TRANSCRIPT
-
SUMMARY OF INFORMATION ON HUMAN CYPENZYMES: HUMAN P450 METABOLISM DATA
Slobodan Rendic*
Faculty of Pharmacy and Biochemistry, University of Zagreb,
A. Kovacica 1, HR 10000 Zagreb, Croatia
SUMMARY
This chapter is an update of the data on substrates, reactions, inducers, and
inhibitors of human CYP enzymes published previously by Rendic and DiCarlo
(1), now covering selection of the literature through 2001 in the reference section.
The data are presented in a tabular form (Table 1) to provide a framework for
predicting and interpreting the new P450 metabolic data. The data are formatted in
an Excel format as most suitable for off-line searching and management of the
Web-database. The data are presented as stated by the author(s) and in the case
when several references are cited the data are presented according to the latest
published information. The searchable database is available either as an Excel file
(for information contact the author), or as a Web-searchable database (Human
P450 Metabolism Database, www.gentest.com) enabling the readers easy and
quick approach to the latest updates on human CYP metabolic reactions.
INTRODUCTION
As reported before (1,3) and discussed in the previous chapters, the
cytochrome P450 (CYP) enzymes catalyze a great number of reactions which have
profound effects on the biological activities of xenobiotics (drugs and
environmental chemicals) and endobiotics (e.g., fatty acids, steroids, prostaglan-
dins, and bile acids). A great number of examples from the literature show that the
83
Copyright q 2002 by Marcel Dekker, Inc. www.dekker.com
*Fax: 385-1-485-6201; E-mail: [email protected]
DRUG METABOLISM REVIEWS, 34(1&2), 83–448 (2002)
-
Ta
ble
1.
Su
mm
ary
of
Info
rmat
ion
on
Hu
man
CY
PE
nzy
mes
Enzy
me
Cat
egory
Subca
tegory
Subst
ance
Rea
ctio
nT
ype
CY
P1
AA
nti
neo
pla
stic
Cy
tokin
eIn
terl
euk
in(I
L)-
6(8
62
)In
hib
ito
r
CY
P1A
Anti
neo
pla
stic
Anti
estr
ogen
,nonst
eroid
al;
P-g
lyco
pro
tein
(P-g
p)
less
po
ten
tin
hib
ito
r
Tam
ox
ifen
(83
7)
Dem
eth
yla
tio
n,
N-
Su
bst
rate
CY
P1A
Anti
neo
pla
stic
Cyto
kin
eT
um
or
nec
rosi
sfa
ctor
(TN
F)-
alpha
(862)
Inhib
itor
CY
P1
AA
nti
vir
alIm
mu
ne-
resp
on
sem
od
ifier
Inte
rfer
on
(IF
N)-
alp
ha
(86
2)
Inh
ibit
or
CY
P1A
Loca
lan
esth
etic
Ben
zoic
acid
este
rN
orc
oca
ine
(125)
Hydro
xyla
tion,
N-
Subst
rate
CY
P1
AP
hy
siolo
gic
al
com
po
und
Cy
tokin
eT
ran
sfo
rmin
gg
row
thfa
cto
r(T
GF
)-b
eta
1(8
62
)
Inh
ibit
or
CY
P1
AS
up
ple
men
tary
dru
gs
and
oth
ersu
bst
ance
s
Nat
ura
lco
mp
ou
nd
,fl
avo
no
idA
cace
tin
(86
0)
Inh
ibit
or
CY
P1
AS
up
ple
men
tary
dru
gs
and
oth
ersu
bst
ance
s
Nat
ura
lco
mp
ou
nd
,fl
avon
oid
,
cate
chin
Ep
icat
ech
in(6
15
)In
hib
ito
r
CY
P1
AS
up
ple
men
tary
dru
gs
and
oth
ersu
bst
ance
s
Cy
tokin
e,p
roin
flam
mat
ory
,
po
lyp
epti
de
Inte
rleu
kin
(IL
)-1
bet
a(8
62
)In
hib
ito
r
CY
P1
AS
up
ple
men
tary
dru
gs
and
oth
ersu
bst
ance
s
Nat
ura
lco
mp
ou
nd
,fl
avon
oid
,
flav
on
ol
My
rcet
in(6
15
)In
du
cer
CY
P1
AS
up
ple
men
tary
dru
gs
and
oth
ersu
bst
ance
s
Uncl
assi
fied
Pro
adif
en,
SK
F-5
25-A
,S
KF
-525A
(17)
Inhib
itor
CY
P1
A1
An
alg
esic
,anti
py
reti
c,
anti
-infl
amm
ato
ry
NS
AID
,p
yra
zolo
ne,
cycl
oo
xy
gen
ase
inh
ibit
or
(les
sp
ote
nt)
Am
inop
yri
ne,
amid
opy
rin
e,
amin
oph
enaz
on
e(1
69
)
Dem
eth
yla
tio
n,
N-
(lo
w
acti
vit
y)
Su
bst
rate
CY
P1
A1
An
alg
esic
,anti
py
reti
c,
anti
-infl
amm
ato
ry
NS
AID
,in
daz
ol,
pro
stag
lan
din
syn
thes
is
inh
ibit
or
Ben
zyd
amin
e(9
62
)O
xid
atio
n,
N-
(min
or
reac
tion)
Su
bst
rate
CY
P1
A1
An
alg
esic
,anti
py
reti
c,
anti
-infl
amm
ato
ry
NS
AID
,p
hen
yla
ceti
cac
id
der
ivat
ive,
cycl
ooxygen
ase-
II
inh
ibit
or
Dic
lofe
nac
,C
H(2
)OH
der
ivat
ive
(77
4)
Hy
dro
xy
lati
on
,C
5-
Su
bst
rate
CY
P1
A1
An
alg
esic
,anti
py
reti
c,
anti
-infl
amm
ato
ry
An
alges
ic,
anti
py
reti
c,
p-a
min
oph
eno
l
Ph
enac
etin
(use
das
test
/mar
ker
sub
stra
te)
(53
,675
,74
7,9
64
)
De-
eth
yla
tio
n,
O-
(ace
tam
inophen
/par
acet
amol
form
atio
n),
use
das
test
/mar
ker
reac
tio
n,
low
KM
Su
bst
rate
RENDIC84
-
CY
P1
A1
An
thel
min
tic
and
anti
fun
gal
Ben
zim
idaz
ole
Thia
ben
daz
ole
(1085)
Induce
r
CY
P1
A1
An
tid
iab
etic
Th
iazo
lid
ined
ion
eT
rog
lita
zon
e(7
23
)Q
uin
on
efo
rmat
ion
(min
or
reac
tion)
Su
bst
rate
CY
P1
A1
An
tifu
ngal
Imid
azo
le;
P-g
lyco
pro
tein
(P-
gp
)in
hib
ito
r
Ket
oco
naz
ole
(po
tent
inhib
ito
r)
(52
8,8
45
,89
2)
Inh
ibit
or
CY
P1
A1
An
tih
ista
min
e
(his
tam
ine
H1
-rec
epto
r
anta
go
nis
t)
Pip
eraz
ine
Cin
nar
izin
e(6
10
)D
ealk
yla
tio
n,
N-
atth
e1
-an
d
4-p
osi
tio
ns
of
the
pip
eraz
ine
rin
g
Su
bst
rate
CY
P1
A1
An
tih
ista
min
e
(his
tam
ine
H1
-rec
epto
r
anta
go
nis
t)
Pip
eraz
ine
Flu
nar
izin
e(6
10
)D
ealk
yla
tio
n,
N-
atth
e1
-an
d
4-p
osi
tio
ns
of
the
pip
eraz
ine
rin
g
Su
bst
rate
CY
P1
A1
An
tim
alar
ial
8-A
min
oq
uin
oli
ne
Pri
maq
uin
e(4
72
)In
du
cer
CY
P1
A1
An
tin
eopla
stic
Ben
zoth
iazo
le2
-(4
-Am
ino
-
3-m
eth
ylp
hen
yl)
ben
zoth
iazo
le(D
F2
03
,
NS
C6
74
49
5)
(95
7)
Hy
dro
xy
lati
on
,C
6-
Su
bst
rate
CY
P1
A1
An
tin
eopla
stic
Ben
zoth
iazo
le2
-(4
-Am
ino
-
3-m
eth
ylp
hen
yl)
ben
zoth
iazo
le(D
F2
03
,
NS
C6
74
49
5)
(95
7)
Ind
uce
r
CY
P1
A1
An
tin
eopla
stic
Ben
zoth
iazo
le2
-(4
-Am
ino
-
3-m
eth
ylp
hen
yl)
ben
zoth
iazo
le(D
F2
03
,
NS
C6
74
49
5)
(95
7)
Inh
ibit
or
CY
P1A
1A
nti
neo
pla
stic
EG
Fre
cepto
rty
rosi
ne
kin
ase
inh
ibit
or
6,7
-bis
-(2
-Met
ho
xy
-eth
ox
y)-
qu
inaz
oli
n-
4-y
l-(3
-eth
yny
l-p
hen
yl)
amin
e,C
P-
35
8,7
74
(50
2)
Qu
inaz
oli
ny
lam
ino
ph
eny
l-
acet
icac
idfo
rmat
ion
Su
bst
rate
CY
P1A
1A
nti
neo
pla
stic
EG
Fre
cepto
rty
rosi
ne
kin
ase
inh
ibit
or
6,7
-bis
-(2
-Met
ho
xy
-eth
ox
y)-
qu
inaz
oli
n-
4-y
l-(3
-eth
yny
l-p
hen
yl)
amin
e,C
P-
35
8,7
74
(50
2)
Dem
eth
yla
tio
n,
O-
Su
bst
rate
(co
nti
nu
ed)
HUMAN P450 METABOLISM DATA 85
-
Ta
ble
1.
Con
tin
ued
Enzy
me
Cat
egory
Subca
tegory
Subst
ance
Rea
ctio
nT
ype
CY
P1A
1A
nti
neo
pla
stic
EG
Fre
cepto
rty
rosi
ne
kin
ase
inh
ibit
or
6,7
-bis
-(2
-Met
ho
xy
-eth
ox
y)-
qu
inaz
oli
n-
4-y
l-(3
-eth
yny
l-p
hen
yl)
amin
e,C
P-
35
8,7
74
(50
2)
Hy
dro
xy
lati
on
,C
-S
ubst
rate
CY
P1A
1A
nti
neo
pla
stic
Pla
tiniu
mbis
-Ace
tato
-am
min
e-dic
hlo
ro-
cycl
oh
exy
lam
ine-
pla
tin
ium
(IV
),JM
21
6
(53
0)
Inh
ibit
or
CY
P1
A1
An
tin
eopla
stic
Alk
yla
tin
gD
acar
baz
ine
(77
8)
Dem
eth
yla
tio
n,
N-
Su
bst
rate
CY
P1
A1
An
tin
eopla
stic
Alk
alo
idE
llip
tici
ne
(9-h
yd
rox
ym
etab
oli
te)
(22
,23)
Inh
ibit
or
CY
P1
A1
An
tin
eopla
stic
Alk
alo
idE
llip
tici
ne
(90
7)
Ox
idat
ion
Su
bst
rate
CY
P1
A1
An
tin
eopla
stic
An
tian
dro
gen
,n
on
ster
oid
alF
luta
mid
e(1
08
1)
Hy
dro
xy
lati
on
,C
2-
Su
bst
rate
CY
P1
A1
An
tin
eopla
stic
His
tam
ine
anta
go
nis
t,
chem
op
ote
nti
atin
g,
cyto
pro
tect
ive;
P-g
lyco
pro
tein
(P-g
p)
inh
ibit
or
N,N
-Die
thy
l-
2-[
4-(
ph
enylm
ethy
l)p
hen
oxy
]
eth
ano
lam
ine
(DP
PE
)(8
76
)
Hy
dro
xy
lati
on
,C
4-
Su
bst
rate
CY
P1
A1
An
tin
eopla
stic
His
tam
ine
anta
go
nis
t,
chem
op
ote
nti
atin
g,
cyto
pro
tect
ive;
P-g
lyco
pro
tein
(P-g
p)
inh
ibit
or
N,N
-Die
thy
l-
2-[
4-(
ph
enylm
ethy
l)p
hen
oxy
]
eth
ano
lam
ine
(DP
PE
)(8
76
)
Dem
eth
yla
tio
n,
N-
Su
bst
rate
CY
P1
A1
An
tin
eopla
stic
Dit
hio
leth
ion
eO
ltip
raz
(wea
kin
hib
ito
r)(6
60
)In
hib
ito
r
CY
P1
A1
An
tin
eopla
stic
Dit
hio
leth
ion
eO
ltip
raz
met
abo
lite
(M)3
(66
0)
Inh
ibit
or
CY
P1
A1
An
tin
eopla
stic
An
ties
tro
gen
,n
on
ster
oid
alT
ore
mif
ene
(17
8)
Dem
eth
yla
tio
n,
N-
Su
bst
rate
CY
P1
A1
An
tip
sych
oti
cD
op
amin
eD
2an
dse
roto
nin
2
(5-H
T2)
rece
pto
ran
tagonis
t,
dib
enzo
thie
pin
e
Zo
tep
ine
(70
4)
Dem
eth
yla
tio
n,
N-
Su
bst
rate
CY
P1
A1
An
tip
sych
oti
cD
op
amin
eD
2an
dse
roto
nin
2
(5-H
T2)
rece
pto
ran
tagonis
t,
dib
enzo
thie
pin
e
Zo
tep
ine
(70
4)
Ox
idat
ion
,S
-S
ubst
rate
RENDIC86
-
CY
P1
A1
An
xio
lyti
c,se
dat
ive,
hy
pn
oti
c
Par
tial
BD
Z-r
ecep
tor
agonis
tA
bec
arnil
(651)
Ben
zyl-
ether
-cle
avag
e
(6-h
yd
rox
y-a
ber
carn
yl
form
atio
n)
Su
bst
rate
CY
P1
A1
An
xio
lyti
c,se
dat
ive,
hy
pn
oti
c
Thia
zole
Clo
met
hia
zole
(682)
Subst
rate
CY
P1A
1C
ardio
vas
cula
rA
nti
arrh
yth
mic
;
P-g
lyco
pro
tein
(P-g
p)
sub
stra
te/l
ess
po
ten
tin
hib
ito
r
Am
iodar
on
e(1
62
)D
e-et
hy
lati
on
,N
-(m
ino
r
reac
tion)
Su
bst
rate
CY
P1A
1C
ardio
vas
cula
rC
alci
um
-chan
nel
blo
cker
,
dih
yd
ropy
rid
ine;
P-g
lyco
pro
tein
(P-g
p)
inh
ibit
or
Am
lodip
ine
(78
2)
Inh
ibit
or
CY
P1A
1C
ardio
vas
cula
rC
alci
um
-chan
nel
blo
cker
,
dih
yd
ropy
rid
ine;
P-g
lyco
pro
tein
(P-g
p)
po
ten
t
inh
ibit
or
Ben
idip
ine
(78
2)
Inh
ibit
or
CY
P1A
1C
ardio
vas
cula
rbet
a-A
dre
noce
pto
rblo
ckin
g
agen
t(b
eta
blo
cker
)
Car
ved
ilo
l(S
)-an
d(R
)-(4
59)
Hydro
xyla
tion
(car
baz
oly
l
C8
-hy
dro
xy
form
atio
n,
min
or
reac
tion)
Su
bst
rate
CY
P1A
1C
ardio
vas
cula
rA
nti
arrh
yth
mic
De-
ethyla
mio
dar
one
(103,7
81)
Inhib
itor
CY
P1A
1C
ardio
vas
cula
rC
alci
um
-chan
nel
blo
cker
,
dih
yd
ropy
rid
ine;
P-g
lyco
pro
tein
(P-g
p)
po
ten
t
inh
ibit
or
Nic
ard
ipin
e(5
05
)O
xid
atio
n(d
ihy
dro
py
rid
ine
ring),
min
or
reac
tion
Su
bst
rate
CY
P1A
1C
ardio
vas
cula
rC
alci
um
-chan
nel
blo
cker
,
dih
yd
ropy
rid
ine;
P-g
lyco
pro
tein
(P-g
p)
less
po
ten
tin
hib
ito
r
Nif
edip
ine
(53
)In
hib
ito
r
CY
P1A
1C
ardio
vas
cula
rC
alci
um
-chan
nel
blo
cker
,
dih
yd
ropy
rid
ine
Pra
nid
ipin
e(d
ehydro
gen
ated
),H
antz
sch
py
ridin
ees
ter
(51
6)
De-
este
rifi
cati
on
(posi
tion
C3
,at
hig
hco
nce
ntr
atio
n)
Su
bst
rate
CY
P1A
1C
ardio
vas
cula
rbet
a-A
dre
noce
pto
rblo
ckin
g
agen
t(b
eta
blo
cker
)
Pro
pra
no
lol
(S)-
,(R
)-(5
8)
Dei
sop
rop
yla
tio
n,
N-
Su
bst
rate
CY
P1A
1C
ardio
vas
cula
rbet
a-A
dre
noce
pto
rblo
ckin
g
agen
t(b
eta
blo
cker
)
Pro
pra
no
lol
(53
)In
hib
ito
r
(co
nti
nu
ed)
HUMAN P450 METABOLISM DATA 87
-
Ta
ble
1.
Con
tin
ued
Enzy
me
Cat
egory
Subca
tegory
Subst
ance
Rea
ctio
nT
ype
CY
P1A
1C
ardio
vas
cula
rA
nti
coag
ula
nt
War
fari
n,
(R)-
,(l
ow
reg
iose
lect
ivit
y)
(14
9)
Hy
dro
xy
lati
on
,C
6-,
C7-,
C8
-S
ubst
rate
CY
P1
A1
Der
mat
olo
gic
alag
ent
An
ti-p
sori
atic
,
ph
oto
sensi
tise
r,
fura
no
coum
arin
Ber
gap
ten
(5-m
eth
oxy
pso
rale
n)
(13
,53)
Inh
ibit
or
CY
P1
A1
Der
mat
olo
gic
alag
ent
An
ti-p
sori
atic
,
ph
oto
sensi
tise
r,
fura
no
coum
arin
Met
ho
xsa
len
(8-m
eth
oxy
pso
rale
n,
xan
tho
tox
in)
(13
,53
,78
8)
Inh
ibit
or
CY
P1A
1D
erm
atolo
gic
alag
ent
Ret
inoic
acid
rece
pto
r
mo
du
lato
r
Ret
inal
,9
-cis
-(8
08
)R
etin
oic
acid
,9
-cis
-
form
atio
n
Su
bst
rate
CY
P1A
1D
erm
atolo
gic
alag
ent
Ret
inoic
acid
rece
pto
r
mo
du
lato
r
Ret
inal
,al
l-tr
an
s-(8
08
)R
etin
oic
acid
,al
l-tr
an
s-
form
atio
n
Su
bst
rate
CY
P1A
1D
erm
atolo
gic
alag
ent
Ret
inoic
acid
rece
pto
r
mo
du
lato
r
Ret
ino
icac
id,
all
tran
s-(t
reti
no
in)
(50
8,1
01
2)
Hy
dro
xy
lati
on
,C
4-,
C1
3ci
s-4
-,C
18
-,4
-ox
o-
form
atio
n,
and
5,6
-ep
ox
idat
ion
Su
bst
rate
CY
P1A
1D
erm
atolo
gic
alag
ent
Ret
inoic
acid
rece
pto
r
mo
du
lato
r
Ret
ino
icac
id,
all
tran
s-(t
reti
no
in)
(62
6,9
12
)
Inh
ibit
or
CY
P1A
1D
erm
atolo
gic
alag
ent
Ret
inoic
acid
rece
pto
r
mo
du
lato
r
Ret
ino
icac
id,
all
tran
s-(t
reti
no
in)
(93
2,1
01
6)
Ind
uce
r
CY
P1
A1
Do
pam
iner
gic
Do
pam
ine
D2
ago
nis
t
(erg
oli
ne
der
ivat
ive)
Lis
uri
de
(61
3)
De-
eth
yla
tio
n,
N-
Su
bst
rate
CY
P1
A1
Do
pam
iner
gic
Do
pam
ine
D2
ago
nis
t(e
rgot
dri
vat
ive)
Ter
gu
rid
e(6
13
)D
e-et
hy
lati
on
,N
-S
ubst
rate
CY
P1
A1
Fo
od
and
foo
d
com
po
nen
ts
Fo
od
Mea
t,ch
arg
rill
ed(7
95
,91
2)
Ind
uce
r
CY
P1
A1
Gas
tro
-in
test
inal
Pro
ton
pu
mp
inh
ibit
or,
ben
zim
idaz
ole
Lan
sop
razo
le(3
7,4
2,4
14)
Ind
uce
r
CY
P1
A1
Gas
tro
-in
test
inal
Pro
ton
pu
mp
inh
ibit
or,
py
rid
iny
lsu
lfin
ylb
enzi
-
mid
azo
le
Om
epra
zole
(po
tent
indu
cer)
(41
,42,8
2,4
15
)
Ind
uce
r
RENDIC88
-
CY
P1
A1
Gas
tro
-in
test
inal
Pro
ton
pu
mp
inh
ibit
or,
ben
zim
idaz
ole
Pan
topra
zole
(lo
win
du
ctio
np
ote
nti
al)
(41
4,4
15
)
Ind
uce
r
CY
P1A
1G
ener
alan
esth
etic
Di-
isopro
pylp
hen
ol
Pro
pofo
l(2
57)
Inhib
itor
CY
P1A
1L
ipid
regula
ting
HM
G-C
oA
reduct
ase
inh
ibit
or
Flu
vas
tati
n(4
88
)H
yd
roxy
lati
on
,C
5-
Su
bst
rate
CY
P1A
1L
oca
lan
esth
etic
Am
ide
type
Ropiv
acai
ne
(S)-
(19
6)
Hy
dro
xy
lati
on
,C
3-,
C4-
(min
or
reac
tio
ns)
Su
bst
rate
CY
P1A
1L
oca
lan
esth
etic
Am
ide
type
Ropiv
acai
ne
(S)-
(19
6)
Dea
lkyla
tio
n,
N-
(Pip
eco
lox
yli
de
20 ,6
0 -fo
rmat
ion
),m
ino
rre
acti
on
Su
bst
rate
CY
P1A
1M
usc
lere
laxan
tC
entr
ally
acti
ng;
P-g
lyco
pro
tein
(P-g
p)
wea
k
inh
ibit
or
Chlo
rzo
xaz
on
e(3
,11
1,1
13
,42
4)
Hy
dro
xy
lati
on
,C
6-
(lo
w
acti
vit
y)
Su
bst
rate
CY
P1
A1
Nu
trit
ion
alag
ents
and
vit
amin
s
Vit
amin
D3
subst
ance
Chole
calc
ifer
ol
(626)
Inhib
itor
CY
P1
A1
Nu
trit
ion
alag
ents
and
vit
amin
s
Vit
amin
Asu
bst
ance
Ret
ino
l(p
ote
nt
inhib
ito
r)(6
26
)In
hib
ito
r
CY
P1
A1
Nu
trit
ion
alag
ents
and
vit
amin
s
Vit
amin
Asu
bst
ance
Ret
ino
l,al
l-tr
an
s-(8
10
)R
etin
al,
all-
tra
ns-
form
atio
n
(hig
hac
tivit
y)
Su
bst
rate
CY
P1
A1
Oth
erch
emic
alP
oly
cycl
icar
om
atic
hy
dro
carb
on
(PA
H)
1-(
1-P
ropy
ny
l)p
yre
ne
(53
7)
Inh
ibit
or
CY
P1
A1
Oth
erch
emic
alB
enze
nes
,ch
lori
nat
ed1
,2-,
1,4
-an
d1
,2,4
-Ch
lori
nat
ed(2
23
)H
yd
roxy
lati
on
,ar
om
atic
Su
bst
rate
CY
P1
A1
Oth
erch
emic
alN
itro
aren
e1
,3-D
init
rop
yre
ne
(10
30
)N
itro
red
uct
ion
Su
bst
rate
CY
P1
A1
Oth
erch
emic
alM
eth
yle
ned
iox
yp
hen
yl
1,4
-Ben
zoth
iazi
nes
,m
echan
ism
bas
ed
inhib
ito
rs(7
83
)
Inh
ibit
or
CY
P1
A1
Oth
erch
emic
alN
itro
aren
e1
,8-D
init
rop
yre
ne
(10
30
)N
itro
red
uct
ion
Su
bst
rate
CY
P1
A1
Oth
erch
emic
alP
oly
cycl
icar
om
atic
hy
dro
carb
on
(PA
H)
11
,12
-Dih
yd
roxy
dib
enzo
[a,l
]py
ren
e
(62
4)
tra
ns-
8,9
-Dio
lfo
rmat
ion
,
pre
fere
nti
alfo
r(+
)-(8
R,9
R)
Su
bst
rate
CY
P1
A1
Oth
erch
emic
alP
oly
cycl
icar
om
atic
hy
dro
carb
on
(PA
H)
1-E
thy
lpy
ren
e(6
91
)H
yd
roxy
lati
on
,b
enzy
lic
Su
bst
rate
CY
P1
A1
Oth
erch
emic
alP
oly
cycl
icar
om
atic
hy
dro
carb
on
(PA
H)
2-(
1-P
ropy
ny
l)p
hen
ath
ren
e(5
37
)In
hib
ito
r
CY
P1A
1O
ther
chem
ical
Het
erocy
clic
,ar
om
atic
amin
e2-A
cety
lam
inofl
uore
ne
(3,3
8)
Induce
r
CY
P1A
1O
ther
chem
ical
Het
erocy
clic
,ar
om
atic
amin
e2-A
cety
lam
inofl
uore
ne
(3,3
9)
Oxid
atio
nS
ubst
rate
(co
nti
nu
ed)
HUMAN P450 METABOLISM DATA 89
-
Ta
ble
1.
Con
tin
ued
Enzy
me
Cat
egory
Subca
tegory
Subst
ance
Rea
ctio
nT
ype
CY
P1A
1O
ther
chem
ical
Het
erocy
clic
,ar
om
atic
amin
e2-A
min
o-1
-met
hyl-
6-p
hen
yli
mid
azo[4
,5-b
]py
ridin
e,P
hIP
(47
1,5
33
)
Hy
dro
xy
lati
on
,N
-S
ubst
rate
CY
P1A
1O
ther
chem
ical
Het
erocy
clic
,ar
om
atic
amin
e2-A
min
o-1
-met
hyl-
6-p
hen
yli
mid
azo[4
,5-b
]py
ridin
e,P
hIP
(47
1)
Hy
dro
xy
lati
on
,C
40 -
Su
bst
rate
CY
P1A
1O
ther
chem
ical
Het
erocy
clic
,ar
om
atic
amin
e2-A
min
o-
3,8
-dim
eth
yli
mid
azo
[4,5
-f]q
uin
ox
alin
e,
MeI
Qx
(53
3,7
08
)
Hy
dro
xy
lati
on
,N
-(m
ino
r
reac
tion)
Su
bst
rate
CY
P1A
1O
ther
chem
ical
Het
erocy
clic
,ar
om
atic
amin
e2-A
min
o-
3-m
eth
yli
mid
azo
[4,5
-f]q
uin
oli
ne,
IQ
(52
8)
Hy
dro
xy
lati
on
,N
-S
ubst
rate
CY
P1
A1
Oth
erch
emic
alA
rom
atic
amin
e2
-Am
ino
anth
race
ne
(55
6)
Ox
idat
ion
Su
bst
rate
CY
P1
A1
Oth
erch
emic
alN
itro
aren
e2
-Nit
ron
aphth
alen
e(7
56
)S
ubst
rate
CY
P1
A1
Oth
erch
emic
alP
oly
chlo
rin
ated
bip
hen
yl
(PC
B)
3,3
0 ,4,4
0 ,5,5
0 -hex
ach
loro
bip
hen
yl
(PC
B
16
9)
(68
4)
Ind
uce
r
CY
P1
A1
Oth
erch
emic
alP
oly
chlo
rin
ated
bip
hen
yl
(PC
B)
3,3
0 ,4,4
0 ,5-p
enta
chlo
rob
iph
enyl
(PC
B
12
6)
(68
4,1
03
4)
Ind
uce
r
CY
P1
A1
Oth
erch
emic
alP
oly
chlo
rin
ated
bip
hen
yl
(PC
B)
3,4
,40 ,5
-tet
rach
loro
bip
hen
yl
(PC
B8
1)
(68
4)
Ind
uce
r
CY
P1
A1
Oth
erch
emic
alP
oly
chlo
rin
ated
bip
hen
yl
(PC
B)
3,4
0 ,5-t
rich
loro
bip
hen
yl
(PC
B3
9)
(68
4)
Ind
uce
r
CY
P1
A1
Oth
erch
emic
alP
orp
hy
rin
og
enic
3,5
-Die
thox
yca
rbo
ny
l-1
,4-d
ihy
dro
-
2,6
-dim
eth
yl-
4-e
thy
lpy
rid
ine
(DD
EP
),
mec
han
ism
bas
edin
hib
ito
r(1
04
3)
Inh
ibit
or
CY
P1A
1O
ther
chem
ical
Porp
hyri
nogen
ic3-[
2-(
2,4
,6-T
rim
ethylp
hen
yl)
thio
ethyl]
-
4-m
eth
yls
yd
no
ne
(TT
MS
),m
echan
ism
bas
edin
hib
ito
r(1
04
3)
Inh
ibit
or
CY
P1
A1
Oth
erch
emic
alF
lav
ono
id,
flav
on
e30 -A
min
o-4
0 -met
ho
xy
flav
on
e(7
86
)In
du
cer
CY
P1
A1
Oth
erch
emic
alF
lav
ono
id,
flav
on
e30 -A
min
o-4
0 -met
ho
xy
flav
on
e(7
86
)In
hib
ito
r
CY
P1
A1
Oth
erch
emic
alA
lky
lox
yco
um
arin
3-C
yan
o-7
-eth
ox
yco
um
arin
(97
3)
De-
eth
yla
tio
n,
O-
Su
bst
rate
RENDIC90
-
CY
P1
A1
Oth
erch
emic
alA
rom
atic
amin
e3
-Met
ho
xy-4
-am
ino
azo
ben
zene
(55
6)
Ox
idat
ion
Su
bst
rate
CY
P1
A1
Oth
erch
emic
alF
lav
ono
id,
flav
on
e30 -M
etho
xy
-40 -n
itro
flav
on
e(7
86
)In
hib
ito
r
CY
P1
A1
Oth
erch
emic
alP
oly
cycl
icar
om
atic
hy
dro
carb
on
(PA
H);
P-g
lyco
pro
tein
(P-g
p)
ind
uce
r/in
hib
ito
r
3-M
eth
ylc
ho
lan
thre
ne,
3M
C,
po
ten
t
indu
cer
(3,3
7,3
9,4
0,2
26
,788
,101
6)
Ind
uce
r
CY
P1
A1
Oth
erch
emic
alT
ob
acco
-sp
ecifi
cn
itro
sam
ine
4-(
Met
hy
lnit
rosa
min
o)-
1-(
3-p
yri
dy
l)-
1-b
uta
no
ne
(NN
K)
(77
2)
Hy
dro
xy
lati
on
,al
ph
a-
met
hy
l/al
ph
a-m
eth
yle
ne
(ket
o
alco
ho
l/k
eto
ald
ehy
de
form
atio
n)
Su
bst
rate
CY
P1
A1
Oth
erch
emic
alF
lav
ono
id,
flav
on
e40 -A
min
o-3
0 -met
ho
xy
flav
on
e(7
86
)In
hib
ito
r
CY
P1
A1
Oth
erch
emic
alA
rom
atic
amin
e4
-Am
ino
bip
hen
yl
(55
6)
Ox
idat
ion
Su
bst
rate
CY
P1
A1
Oth
erch
emic
alF
lav
ono
id,
flav
on
e40 -A
min
ofl
avo
ne
(78
5)
Ind
uce
r
CY
P1
A1
Oth
erch
emic
alF
lav
ono
id,
flav
on
e40 -I
od
ofl
avo
ne(
785
)In
hib
ito
r
CY
P1
A1
Oth
erch
emic
alF
lav
ono
id,
flav
on
e40 -M
etho
xy
-30 -n
itro
flav
on
e(7
86
)In
du
cer
CY
P1
A1
Oth
erch
emic
alF
lav
ono
id,
flav
on
e40 -M
etho
xy
-30 -n
itro
flav
on
e(7
86
)In
hib
ito
r
CY
P1
A1
Oth
erch
emic
alF
lav
ono
id,
flav
on
e5
,6-B
F(5
,6-b
enzo
flav
on
e,b
eta-
nap
hth
ofl
avo
ne)
(39
,63
)
Ind
uce
r
CY
P1A
1O
ther
chem
ical
Aro
mat
icam
ine
6-A
min
och
ryse
ne
(556)
Oxid
atio
n(h
igh
acti
vit
y)
Subst
rate
CY
P1
A1
Oth
erch
emic
alA
rom
atic
amin
e6
-Am
ino
chry
sen
e-1
,2-d
iol
(as
met
abo
lite
of
6-a
min
och
ryse
ne)
(49
)
Dio
lep
oxid
efo
rmat
ion
Su
bst
rate
CY
P1A
1O
ther
chem
ical
Nit
roar
ene
6-N
itro
chry
sene
(558)
tra
ns-
1,2
-Dih
yd
ro-
1,2
-dih
yd
rox
yfo
rmat
ion
(rin
g
ox
idat
ion
)
Su
bst
rate
CY
P1A
1O
ther
chem
ical
Nit
roar
ene
6-N
itro
chry
sene
(956)
Induce
r
CY
P1
A1
Oth
erch
emic
alP
oly
cycl
icar
om
atic
hy
dro
carb
on
(PA
H)
7,1
2-D
imet
hy
lben
z[a
]an
thra
cen
e
(DM
BA
)(5
56
,61
2)
Dio
lfo
rmat
ion
and
CH
3-h
yd
roxy
lati
on
(hig
h
acti
vit
y)
Su
bst
rate
CY
P1
A1
Oth
erch
emic
alP
oly
cycl
icar
om
atic
hy
dro
carb
on
(PA
H)
7,1
2-D
imet
hy
lben
z[a
]an
thra
cen
e
(DM
BA
)(6
12
,79
0,1
01
6)
Ind
uce
r
CY
P1
A1
Oth
erch
emic
alP
oly
cycl
icar
om
atic
hy
dro
carb
on
(PA
H)
7,1
2-D
imet
hy
lben
z[a
]an
thra
cen
e-
3,4
-dio
l(D
MB
A-3
,4-d
iol)
(37
,55
6,6
12
)
Ox
idat
ion
Su
bst
rate
(co
nti
nu
ed)
HUMAN P450 METABOLISM DATA 91
-
Ta
ble
1.
Con
tin
ued
Enzy
me
Cat
egory
Subca
tegory
Subst
ance
Rea
ctio
nT
ype
CY
P1
A1
Oth
erch
emic
alF
lav
ono
id,
flav
on
e7
,8-B
F(7
,8-b
enzo
flav
on
e,al
pha-
nap
hth
ofl
avone)
,pote
nt,
sele
ctiv
e
inhib
ito
r(3
,15
,23
,37
,58,6
6,6
9,8
3,2
66,
32
9,3
73
,42
3,4
26
,42
7,5
37
,78
8,8
92
,95
6)
Inh
ibit
or
CY
P1
A1
Oth
erch
emic
alF
lav
ono
id,
flav
on
e7
,8-B
F(7
,8-b
enzo
flav
on
e,al
pha-
nap
hth
ofl
avo
ne)
(37
3)
Ind
uce
r
CY
P1
A1
Oth
erch
emic
alP
oly
cycl
icar
om
atic
hy
dro
carb
on
(PA
H)
7,8
-Dih
yd
rox
yb
enzo
[a]p
yre
ne
(7,8
-dih
yd
rodio
l)(4
56
,55
0)
Tet
rols
and
trio
lsfo
rmat
ion
(hig
hac
tivit
y)
Su
bst
rate
CY
P1
A1
Oth
erch
emic
alA
lky
lox
yco
um
arin
7-E
tho
xy
-4-t
rifl
uo
rom
eth
ylc
oum
arin
(77
2)
De-
eth
yla
tio
n,
O-
(med
ium
KM
)
Su
bst
rate
CY
P1
A1
Oth
erch
emic
alA
lky
lox
yco
um
arin
7-E
tho
xy
cou
mar
in(2
36
,62
6,7
62
)D
e-et
hy
lati
on
,O
-S
ubst
rate
CY
P1
A1
Oth
erch
emic
alA
lky
lox
yre
soru
fin
7-E
tho
xy
reso
rufi
n(3
,11
,39
,224
,
23
6,3
28
,41
5,8
29
,77
2,9
73
)
De-
eth
yla
tio
n,
O-
(lo
wK
M,
use
das
test
/mar
ker
reac
tion)
Su
bst
rate
CY
P1
A1
Oth
erch
emic
alA
lky
lox
yre
soru
fin
7-E
tho
xy
reso
rufi
n(5
3,5
8)
Inh
ibit
or
CY
P1A
1O
ther
chem
ical
Car
baz
ole
7H
-dib
enzo
[c,g
]car
baz
ole
(DB
C)
(948)
Oxid
atio
nS
ubst
rate
CY
P1
A1
Oth
erch
emic
alA
za-a
rom
atic
7M
BA
C(7
-Met
hy
lben
z[c
]acr
idin
e)(3
5)
Ox
idat
ion
Su
bst
rate
CY
P1
A1
Oth
erch
emic
alA
lky
lox
yre
soru
fin
7-M
eth
ox
yre
soru
fin
(46
3,4
64
)D
emet
hy
lati
on
,O
-(u
sed
as
test
/mar
ker
reac
tio
n)
Su
bst
rate
CY
P1
A1
Oth
erch
emic
alP
oly
cycl
icar
om
atic
hy
dro
carb
on
(PA
H)
8,9
-Dih
yd
rox
yd
iben
zo[a
,l]p
yre
ne
(62
4)
(2)-
11
,12-T
etro
l,(R
,R)-
form
atio
n
Su
bst
rate
CY
P1A
1O
ther
chem
ical
Org
anic
solv
ents
Ace
tonit
rile
(619)
Inhib
itor
CY
P1
A1
Oth
erch
emic
alP
oly
cycl
icar
om
atic
hy
dro
carb
on
(PA
H)
Ace
tyle
nes
(53
7)
Inh
ibit
or
CY
P1
A1
Oth
erch
emic
alP
oly
cycl
icar
om
atic
hy
dro
carb
on
(PA
H)
Ben
z[a
]anth
race
ne
(39
,528
,98
9)
Ind
uce
r
CY
P1
A1
Oth
erch
emic
alP
oly
cycl
icar
om
atic
hy
dro
carb
on
(PA
H)
Ben
zo[a
]per
yle
ne
(82
6)
Ox
idat
ion
Su
bst
rate
CY
P1
A1
Oth
erch
emic
alP
oly
cycl
icar
om
atic
hy
dro
carb
on
(PA
H)
Ben
zo[a
]pyre
ne
(cig
aret
tesm
oke)
(3,7
,14
,37,3
9,4
7,4
58
,103
6)
Ind
uce
r
RENDIC92
-
CY
P1
A1
Oth
erch
emic
alP
oly
cycl
icar
om
atic
hy
dro
carb
on
(PA
H)
Ben
zo[a
]py
ren
e(1
8,5
1,1
81,4
56,5
50)
Hy
dro
xy
lati
on
3-,
9-,
7-
and
dih
yd
rodio
ls7
,8-,
9,1
0-,
4,5
-
form
atio
n(h
igh
acti
vit
y)
Su
bst
rate
CY
P1
A1
Oth
erch
emic
alP
oly
cycl
icar
om
atic
hy
dro
carb
on
(PA
H)
Ben
zo[a
]py
ren
e(6
69
)tr
an
s-7
,8-D
ihy
dro
xy-
7,8
-dih
yd
ro-
form
atio
n(l
ow
acti
vit
y)
Su
bst
rate
CY
P1
A1
Oth
erch
emic
alP
oly
cycl
icar
om
atic
hy
dro
carb
on
(PA
H)
Ben
zo[b
]flu
ora
nth
ene
(98
9)
Ind
uce
r
CY
P1
A1
Oth
erch
emic
alP
oly
cycl
icar
om
atic
hy
dro
carb
on
(PA
H)
Ben
zo[b
]flu
ora
nth
ene-
9,1
0-d
iol
(55
6)
Ox
idat
ion
Su
bst
rate
CY
P1
A1
Oth
erch
emic
alP
oly
cycl
icar
om
atic
hy
dro
carb
on
(PA
H)
Ben
zo[b
]per
yle
ne
(82
6)
Ox
idat
ion
Su
bst
rate
CY
P1
A1
Oth
erch
emic
alP
oly
cycl
icar
om
atic
hy
dro
carb
on
(PA
H)
Ben
zo[g
,h,i
]per
yle
ne
(10
36)
Ind
uce
r
CY
P1
A1
Oth
erch
emic
alP
oly
cycl
icar
om
atic
hy
dro
carb
on
(PA
H)
Ben
zo[k
]flu
ora
nth
ene
(98
9)
Ind
uce
r
CY
P1
A1
Oth
erch
emic
alA
za-a
rom
atic
Dib
enz[
a,j
]acr
idin
e,D
BA
JAC
(35
)O
xid
atio
nS
ubst
rate
CY
P1
A1
Oth
erch
emic
alP
oly
cycl
icar
om
atic
hy
dro
carb
on
(PA
H)
Dib
enzo
[a,e
]flu
ora
nth
ene
(82
6)
Ox
idat
ion
Su
bst
rate
CY
P1
A1
Oth
erch
emic
alP
oly
cycl
icar
om
atic
hy
dro
carb
on
(PA
H)
Dib
enzo
[a,f
]flu
ora
nth
ene
(82
6)
Ox
idat
ion
Su
bst
rate
CY
P1
A1
Oth
erch
emic
alP
oly
cycl
icar
om
atic
hy
dro
carb
on
(PA
H)
Dib
enzo
[a,h
]anth
race
ne
(98
9)
Ind
uce
r
CY
P1
A1
Oth
erch
emic
alP
oly
cycl
icar
om
atic
hy
dro
carb
on
(PA
H)
Dib
enzo
[a,h
]py
ren
e(8
26
)O
xid
atio
nS
ubst
rate
CY
P1
A1
Oth
erch
emic
alP
oly
cycl
icar
om
atic
hy
dro
carb
on
(PA
H)
Dib
enzo
[a,i
]py
ren
e(8
26
)O
xid
atio
nS
ubst
rate
CY
P1
A1
Oth
erch
emic
alP
oly
cycl
icar
om
atic
hy
dro
carb
on
(PA
H)
Dib
enzo
[a,l
]py
ren
e(6
24
,75
0)
11
,12
-Dih
yd
rod
iol-
13
,14
-ep
oxid
efo
rmat
ion
(hig
hac
tivit
y,
ster
eo-
and
reg
iose
lect
ivit
y)
Su
bst
rate
CY
P1
A1
Oth
erch
emic
alP
oly
cycl
icar
om
atic
hy
dro
carb
on
(PA
H)
Dib
enzo
[j,
l]fl
uora
nth
ene
(82
6)
Ox
idat
ion
Su
bst
rate
CY
P1A
1O
ther
chem
ical
Org
anic
solv
ents
,A
lcohol
Eth
anol
(619)
Inhib
itor
(co
nti
nu
ed)
HUMAN P450 METABOLISM DATA 93
-
Ta
ble
1.
Con
tin
ued
Enzy
me
Cat
egory
Subca
tegory
Subst
ance
Rea
ctio
nT
ype
CY
P1A
1O
ther
chem
ical
Uncl
assi
fied
Indolo
[3,2
-b]c
arbaz
ole
(50,3
49)
Induce
r
CY
P1
A1
Oth
erch
emic
alB
enzo
dio
xo
leIs
osa
fro
le(2
24
)In
du
cer
CY
P1
A1
Oth
erch
emic
alB
enzo
dio
xo
leIs
osa
fro
le(2
24
)In
hib
ito
r
CY
P1
A1
Oth
erch
emic
alM
etal
sM
etal
ions
(Ca,
Pb
,H
g,
Cd
)(9
89
)In
hib
ito
r
CY
P1A
1O
ther
chem
ical
Org
anic
solv
ents
,A
lcohol
Met
han
ol
(wea
kin
hib
itor)
(619)
Inhib
itor
CY
P1
A1
Oth
erch
emic
alP
oly
cycl
icar
om
atic
hy
dro
carb
on
s(P
AH
s)
Moto
rcycl
eex
hau
stpar
ticu
late
(914)
Induce
r
CY
P1
A1
Oth
erch
emic
alP
oly
cycl
icar
om
atic
hy
dro
carb
on
(PA
H)
Nap
hth
o[1
,2-b
]flu
ora
nth
ene
(82
6)
Ox
idat
ion
Su
bst
rate
CY
P1
A1
Oth
erch
emic
alP
oly
cycl
icar
om
atic
hy
dro
carb
on
(PA
H)
Nap
hth
o[2
,3-a
]py
ren
e(8
26
)O
xid
atio
nS
ubst
rate
CY
P1
A1
Oth
erch
emic
alP
oly
cycl
icar
om
atic
hy
dro
carb
on
(PA
H)
Nap
hth
o[2
,3-e
]py
ren
e(8
26
)O
xid
atio
nS
ubst
rate
CY
P1A
1O
ther
chem
ical
Het
erocy
clic
,ar
om
atic
amin
eN
-Hy
dro
xy-2
-am
ino
-1-m
eth
yl-
6-p
hen
yli
mid
azo[4
,5-b
]py
ridin
e,
N-h
yd
roxy
Ph
IP(5
33
)
Ox
idat
ion
Su
bst
rate
CY
P1A
1O
ther
chem
ical
Car
baz
ole
N-m
eth
yld
iben
zo[c
,g]c
arbaz
ole
(MeD
BC
)(9
48
)
Ox
idat
ion
Su
bst
rate
CY
P1
A1
Oth
erch
emic
alA
zoar
om
atic
amin
eo-A
min
oaz
oto
luen
e(5
56
)O
xid
atio
nS
ubst
rate
CY
P1
A1
Oth
erch
emic
alF
lav
ono
idP
D9
80
59
(78
7)
Inh
ibit
or
CY
P1
A1
Oth
erch
emic
alP
oly
cycl
icar
om
atic
hy
dro
carb
on
(PA
H)
Ph
enan
thre
ne
(60
5)
Dih
yd
rod
iol,
C9
,10
-fo
rmat
ion
(hig
h
acti
vit
y)
Su
bst
rate
CY
P1
A1
Oth
erch
emic
alQ
uin
on
esQ
uin
on
es(3
)O
xid
atio
nS
ubst
rate
CY
P1
A1
Oth
erch
emic
alD
iox
in,H
alo
gen
ated
arom
atic
hy
dro
carb
on
;P
-gly
copro
tein
(P-g
p)
ind
uce
r/in
hib
ito
r
TC
DD
(2,3
,7,8
-Tet
rach
loro
dib
enzo
-
p-d
ioxin
)(1
,3,3
9,4
0,5
0,2
26
,34
9,4
48
,
61
2,8
78
,10
34
)
Ind
uce
r
CY
P1A
1O
ther
chem
ical
Org
anic
solv
ents
,ar
om
atic
Tolu
ene
(457)
Hydro
xyla
tion,
CH
3-
(ben
zyl
alco
ho
lfo
rmat
ion
)
Su
bst
rate
RENDIC94
-
CY
P1A
1O
ther
chem
ical
Org
anic
solv
ents
,ar
om
atic
Tolu
ene
(87,2
98)
Hydro
xyla
tion,
par
a-(c
reso
l,
p-
form
atio
n,
min
or
met
abo
lite
)
Su
bst
rate
CY
P1A
1O
ther
chem
ical
Org
anic
solv
ents
,hal
ogen
ated
alk
ene
Tri
chlo
roet
hyle
ne,
TC
E(5
79
,10
42
)C
hlo
ral
hy
dra
tefo
rmat
ion
(min
or
enzy
me)
Su
bst
rate
CY
P1
A1
Oth
erch
emic
alN
on
ion
icp
hen
oli
cd
eter
gen
tT
rito
nN
-10
1(5
27
)H
yd
roxy
lati
on
,al
ky
l-(l
ow
exte
nt)
Su
bst
rate
CY
P1
A1
Pes
tici
de
Inse
ctic
ide,
carb
amat
eC
arb
ary
l(7
88
,10
85
)In
du
cer
CY
P1
A1
Pes
tici
de
Inse
ctic
ide,
ben
zoylp
hen
yl
ure
a,ch
itin
syn
thes
isin
hib
ito
r
Difl
ub
enzu
ron
(91
5)
Inh
ibit
or
CY
P1
A1
Pes
tici
de
Fu
ng
icid
eF
ura
met
py
r(1
01
0)
Dem
eth
yla
tio
n,
N-
Su
bst
rate
CY
P1
A1
Ph
ysi
olo
gic
al
com
po
und
Fat
tyac
idA
rach
ido
nic
acid
(62
6)
Inh
ibit
or
CY
P1
A1
Ph
ysi
olo
gic
al
com
po
und
Ind
ole
Ind
ola
ceti
cac
id(7
89
)In
du
cer
CY
P1
A1
Ph
ysi
olo
gic
al
com
po
und
Neu
rotr
ansm
itte
r,
ind
ole
amin
e
Try
pta
min
e(7
89
)In
du
cer
CY
P1
A1
Ph
ysi
olo
gic
al
com
po
und
Neu
rotr
ansm
itte
r,
ind
ole
amin
e
Try
pta
min
e(7
89
)S
ubst
rate
CY
P1
A1
Ph
ysi
olo
gic
al
com
po
und
Po
rph
yri
no
gen
Uro
po
rphy
rin
og
en(7
58
)O
xid
atio
n(u
rop
horp
hy
rin
form
atio
n),
min
or
reac
tio
n
Su
bst
rate
CY
P1
A1
Sex
ho
rmo
ne
An
dro
gen
and
anab
oli
cA
nd
rost
ened
ion
e(3
09
)H
yd
roxy
lati
on
,C
6b
eta-
Su
bst
rate
CY
P1
A1
Sex
ho
rmo
ne
Ox
yst
ero
lD
ehy
dro
epia
nd
rost
ero
ne,
DH
EA
(77
3)
Inh
ibit
or
CY
P1
A1
Sex
ho
rmo
ne
Est
rog
enE
stra
dio
l3
-met
hyl
eth
er(4
45
)D
emet
hy
lati
on
,O
-S
ubst
rate
CY
P1
A1
Sex
ho
rmo
ne
Est
rog
enE
stra
dio
l,1
7b
eta-
(30
8,6
56
,10
08
)H
yd
roxy
lati
on
,C
2-
(maj
or
reac
tion,
low
KM
,h
igh
acti
vit
y)
Su
bst
rate
CY
P1
A1
Sex
ho
rmo
ne
Est
rog
enE
stra
dio
l,1
7b
eta-
(4,1
3,5
0,
68
4,1
00
8)
Hy
dro
xy
lati
on
,C
4-
(min
or
reac
tion,
low
KM
,lo
w
acti
vit
y)
Su
bst
rate
CY
P1
A1
Sex
ho
rmo
ne
Est
rog
enE
stra
dio
l,1
7b
eta-
(4,1
3,5
0)
Hy
dro
xy
lati
on
,C
6al
pha-
Su
bst
rate
CY
P1
A1
Sex
ho
rmo
ne
Est
rog
enE
stra
dio
l,1
7b
eta-
(4,1
3,5
0)
Hy
dro
xy
lati
on
,C
15
alph
a-S
ubst
rate
CY
P1
A1
Sex
ho
rmo
ne
Est
rog
enE
stra
dio
l,1
7b
eta-
(81
3)
Qu
ino
lfo
rmat
ion
Su
bst
rate
CY
P1
A1
Sex
ho
rmo
ne
Est
rog
enE
stro
ne
(30
7)
Qu
ino
lfo
rmat
ion
Su
bst
rate
(co
nti
nu
ed)
HUMAN P450 METABOLISM DATA 95
-
Ta
ble
1.
Con
tin
ued
Enzy
me
Cat
egory
Subca
tegory
Subst
ance
Rea
ctio
nT
ype
CY
P1
A1
Sex
ho
rmo
ne
Ste
roid
Pre
gnen
olo
ne
(30
8)
Hy
dro
xy
lati
on
,C
16
alph
a-
(hig
hac
tivit
y)
Su
bst
rate
CY
P1
A1
Sex
ho
rmo
ne
Ste
roid
Pre
gnen
olo
ne
(30
8)
Hy
dro
xy
lati
on
,C
17
alph
a-
(lo
wac
tiv
ity
)
Su
bst
rate
CY
P1
A1
Sex
ho
rmo
ne
Ste
roid
Pre
gnen
olo
ne
(54
9)
Hy
dro
xy
lati
on
,C
7b
eta-
Su
bst
rate
CY
P1
A1
Sex
ho
rmo
ne
Pro
ges
tag
en;
P-g
lyco
pro
tein
(P-g
p)
inh
ibit
or
Pro
ges
tero
ne
(30
8,3
09
,95
8)
Hy
dro
xy
lati
on
,C
6b
eta-
(hig
h
acti
vit
y)
Su
bst
rate
CY
P1
A1
Sex
ho
rmo
ne
Pro
ges
tag
en;
P-g
lyco
pro
tein
(P-g
p)
inh
ibit
or
Pro
ges
tero
ne
(30
8,3
09
,95
8)
Hy
dro
xy
lati
on
,C
16
alph
a-S
ubst
rate
CY
P1
A1
Sex
ho
rmo
ne
An
dro
gen
and
anab
oli
cT
esto
ster
on
e(3
09
,95
8)
Hy
dro
xy
lati
on
,C
6b
eta-
(hig
h
acti
vit
y)
Su
bst
rate
CY
P1
A1
Sti
mu
lan
tsan
d
ano
rect
ic
Hal
luci
no
gen
ic3
,4-M
eth
yle
ned
iox
yet
hy
lam
phet
amin
e
(R,S
)-(E
ve,
MD
E)
(84
7)
Dem
eth
yle
nat
ion
,O
-(h
igh
acti
vit
y)
Su
bst
rate
CY
P1
A1
Sti
mu
lan
tsan
d
ano
rect
ic
Hal
luci
no
gen
ic3
,4-M
eth
yle
ned
iox
yet
hy
lam
phet
amin
e
(R,S
)-(E
ve,
MD
E)
(84
7)
De-
eth
yla
tio
n,
N-
(hig
h
acti
vit
y)
Su
bst
rate
CY
P1
A1
Su
pp
lem
enta
ryd
rug
s
and
oth
ersu
bst
ance
s
Ho
psu
bst
ance
s,p
ren
yla
ted
flav
onoid
,ch
alco
ne
20 ,4
0 ,60 ,4
-Tet
rah
yd
roxy
-30 -
pre
ny
lch
alco
ne
(87
5)
Inh
ibit
or
CY
P1
A1
Su
pp
lem
enta
ryd
rug
s
and
oth
ersu
bst
ance
s
Ho
psu
bst
ance
s,p
ren
yla
ted
flav
on
oid
,fl
avan
on
e
6,8
-Dip
ren
yln
arin
gen
in,
po
ten
tin
hib
ito
r
(87
5)
Inh
ibit
or
CY
P1
A1
Su
pp
lem
enta
ryd
rug
s
and
oth
ersu
bst
ance
s
Ho
psu
bst
ance
s,p
ren
yla
ted
flav
on
oid
,fl
avan
on
e
6-P
ren
yln
arin
gen
in,
po
ten
tin
hib
ito
r
(87
5)
Inh
ibit
or
CY
P1
A1
Su
pp
lem
enta
ryd
rug
s
and
oth
ersu
bst
ance
s
Ho
psu
bst
ance
s,p
ren
yla
ted
flav
on
oid
,fl
avan
on
e
8-P
ren
yln
arin
gen
in,
po
ten
tin
hib
ito
r
(87
5)
Inh
ibit
or
CY
P1
A1
Su
pp
lem
enta
ryd
rug
s
and
oth
ersu
bst
ance
s
Nat
ura
lco
mp
ou
nd
,
my
coto
xin
Afl
ato
xin
B1
(77
2)
Ep
oxid
atio
nS
ubst
rate
CY
P1
A1
Su
pp
lem
enta
ryd
rug
s
and
oth
ersu
bst
ance
s
Gra
pef
ruit
juic
esu
bst
ance
s,
flav
on
oid
,fl
avo
ne
Ap
igen
in(3
73
)In
hib
ito
r
CY
P1
A1
Su
pp
lem
enta
ryd
rug
s
and
oth
ersu
bst
ance
s
Bra
ssic
aveg
etab
les
Bra
ssic
aveg
etab
les
(898)
Induct
ion
CY
P1
A1
Su
pp
lem
enta
ryd
rug
s
and
oth
ersu
bst
ance
s
Nat
ura
lco
mp
ou
nd
,fl
avon
oid
,
flav
on
e
Chry
sin
(13
,44)
Inh
ibit
or
RENDIC96
-
CY
P1
A1
Su
pp
lem
enta
ryd
rug
s
and
oth
ersu
bst
ance
s
Nat
ura
lco
mp
ou
nd
,co
lori
ng
agen
t,C
hem
op
rev
enti
ve
Curc
um
in(7
90
)In
du
cer
CY
P1
A1
Su
pp
lem
enta
ryd
rug
s
and
oth
ersu
bst
ance
s
Nat
ura
lco
mp
ou
nd
,co
lori
ng
agen
t,C
hem
op
rev
enti
ve
Curc
um
in(7
90
)In
hib
ito
r
CY
P1
A1
Su
pp
lem
enta
ryd
rug
s
and
oth
ersu
bst
ance
s
Ho
psu
bst
ance
s,p
ren
yla
ted
flav
onoid
,ch
alco
ne
Deh
yd
rocy
clo
xan
tho
hum
ol
(87
5)
Inh
ibit
or
CY
P1
A1
Su
pp
lem
enta
ryd
rug
s
and
oth
ersu
bst
ance
s
Ho
psu
bst
ance
s,p
ren
yla
ted
flav
on
oid
,C
hal
cone
Deh
yd
rocy
clo
xan
tho
hum
olh
yd
rate
(87
5)
Inh
ibit
or
CY
P1
A1
Su
pp
lem
enta
ryd
rug
s
and
oth
ersu
bst
ance
s
An
tial
coh
oli
c;P
-gly
copro
tein
(P-g
p)
inh
ibit
or
Die
thy
ldit
hio
carb
amat
eas
met
abo
lite
of
dis
ulfi
ram
(69
)
Inh
ibit
or
CY
P1
A1
Su
pp
lem
enta
ryd
rug
s
and
oth
ersu
bst
ance
s
Cit
rus
fruit
com
po
und
,
flav
on
oid
agli
con
e
Dio
smet
in(7
79
,86
0)
Ind
uce
r
CY
P1
A1
Su
pp
lem
enta
ryd
rug
s
and
oth
ersu
bst
ance
s
Cit
rus
fruit
com
po
und
,
flav
on
oid
agli
con
e
Dio
smet
in(7
79
)In
hib
ito
r
CY
P1
A1
Su
pp
lem
enta
ryd
rug
s
and
oth
ersu
bst
ance
s
Fla
vo
no
idD
iosm
in(7
79
)In
du
cer
CY
P1
A1
Su
pp
lem
enta
ryd
rug
s
and
oth
ersu
bst
ance
s
Nat
ura
lco
mp
ou
nd
,fl
avon
oid
,
flav
ano
ne
Eri
od
icty
ol
(86
0)
Su
bst
rate
CY
P1
A1
Su
pp
lem
enta
ryd
rug
s
and
oth
ersu
bst
ance
s
Nat
ura
lco
mp
ou
nd
,fl
avon
oid
,
flav
ano
ne
Fla
van
on
e(7
87
)In
hib
ito
r
CY
P1
A1
Su
pp
lem
enta
ryd
rug
s
and
oth
ersu
bst
ance
s
Nat
ura
lco
mp
ou
nd
,fl
avo
no
idF
lav
on
e(4
64
,78
7)
Inh
ibit
or
CY
P1
A1
Su
pp
lem
enta
ryd
rug
s
and
oth
ersu
bst
ance
s
Nat
ura
lco
mp
ou
nd
,fl
avon
oid
,
flav
on
e
Fla
vo
ne,
C3,7
-hy
dro
xy
(46
4)
Inh
ibit
or
CY
P1
A1
Su
pp
lem
enta
ryd
rug
s
and
oth
ersu
bst
ance
s
Nat
ura
lco
mp
ou
nd
,fl
avon
oid
,
flav
on
e
Fla
vo
ne,
C3-h
yd
roxy
(46
3)
Inh
ibit
or
CY
P1
A1
Su
pp
lem
enta
ryd
rug
s
and
oth
ersu
bst
ance
s
Nat
ura
lco
mp
ou
nd
,fl
avon
oid
,
flav
on
e
Fla
vo
ne,
C5-h
yd
roxy
(46
4)
Inh
ibit
or
CY
P1
A1
Su
pp
lem
enta
ryd
rug
s
and
oth
ersu
bst
ance
s
Nat
ura
lco
mp
ou
nd
,fl
avon
oid
,
flav
on
e
Fla
vone,
C7-h
ydro
xy
(hig
hse
lect
ivit
y
inhib
ito
r)(4
64
)
Inh
ibit
or
CY
P1
A1
Su
pp
lem
enta
ryd
rug
s
and
oth
ersu
bst
ance
s
Nat
ura
lco
mp
ou
nd
,fl
avon
oid
,
flav
on
ol
Gal
ang
in(l
ow
po
ten
cyin
du
cer)
(61
2)
Ind
uce
r
CY
P1
A1
Su
pp
lem
enta
ryd
rug
s
and
oth
ersu
bst
ance
s
Nat
ura
lco
mp
ou
nd
,
Fla
vo
no
id,
Fla
vo
no
l
Gal
ang
in(4
64
,61
2)
Inh
ibit
or
(co
nti
nu
ed)
HUMAN P450 METABOLISM DATA 97
-
Ta
ble
1.
Con
tin
ued
Enzy
me
Cat
egory
Subca
tegory
Subst
ance
Rea
ctio
nT
ype
CY
P1
A1
Su
pp
lem
enta
ryd
rug
s
and
oth
ersu
bst
ance
s
Nat
ura
lco
mp
ou
nd
,
Fla
vo
no
id,
Fla
vo
no
l
Gal
ang
in(9
94
)H
yd
roxy
lati
on
,ri
ng
Su
bst
rate
CY
P1
A1
Su
pp
lem
enta
ryd
rug
s
and
oth
ersu
bst
ance
s
Nat
ura
lco
mp
ou
nd
,S
oy
bea
ns
flav
on
oid
,is
ofl
avon
e
Gen
iste
in(6
70
)30 ,4
0 ,5,7
-tet
rah
ydro
xy
iso
-
flav
on
e(o
rbo
l)fo
rmat
ion
Su
bst
rate
CY
P1
A1
Su
pp
lem
enta
ryd
rug
s
and
oth
ersu
bst
ance
s
Nat
ura
lco
mpound,
soybea
ns
flav
on
oid
,is
ofl
avon
e
Gen
iste
in(6
70
)H
yd
roxy
lati
on
,C
6-
(min
or
reac
tion)
Su
bst
rate
CY
P1
A1
Su
pp
lem
enta
ryd
rug
s
and
oth
ersu
bst
ance
s
Nat
ura
lco
mpound,
soybea
ns
flav
on
oid
,is
ofl
avon
e
Gen
iste
in(6
70
)H
yd
roxy
lati
on
,C
8-
(min
or
reac
tion)
Su
bst
rate
CY
P1
A1
Su
pp
lem
enta
ryd
rug
s
and
oth
ersu
bst
ance
s
Nat
ura
lco
mpound,
soybea
ns
flav
on
oid
,is
ofl
avon
e
Gen
iste
in,
less
po
ten
tin
hib
ito
r(8
75
)In
hib
ito
r
CY
P1
A1
Su
pp
lem
enta
ryd
rug
s
and
oth
ersu
bst
ance
s
Nat
ura
lco
mp
ou
nd
,fl
avo
no
idH
esp
eret
in(8
60
)In
hib
ito
r
CY
P1
A1
Su
pp
lem
enta
ryd
rug
s
and
oth
ersu
bst
ance
s
Nat
ura
lco
mp
ou
nd
,fl
avo
no
idH
esp
eret
in(8
60
)D
emet
hy
lati
on
,O
-(t
o
erio
dic
tyo
l)
Su
bst
rate
CY
P1
A1
Su
pp
lem
enta
ryd
rug
s
and
oth
ersu
bst
ance
s
Nat
ura
lco
mp
ou
nd
,fl
avon
oid
,
flav
ano
ne
Ho
mo
erio
dic
tyo
l(8
60
)In
hib
ito
r
CY
P1
A1
Su
pp
lem
enta
ryd
rug
s
and
oth
ersu
bst
ance
s
Ho
psu
bst
ance
s,p
ren
yla
ted
flav
onoid
,ch
alco
ne
Iso
xan
tho
hum
ol
(87
5)
Inh
ibit
or
CY
P1
A1
Su
pp
lem
enta
ryd
rug
s
and
oth
ersu
bst
ance
s
Nat
ura
lco
mp
ou
nd
,
Fla
vo
no
id,
Fla
vo
no
l
Kae
mp
feri
de
(99
4)
Hy
dro
xy
lati
on
,ri
ng
Su
bst
rate
CY
P1
A1
Su
pp
lem
enta
ryd
rug
s
and
oth
ersu
bst
ance
s
Nat
ura
lco
mp
ou
nd
,fl
avon
oid
,
flav
on
ol
Kae
mp
fero
l(1
3,4
4,7
80)
Inh
ibit
or
CY
P1
A1
Su
pp
lem
enta
ryd
rug
s
and
oth
ersu
bst
ance
s
Nat
ura
lco
mp
ou
nd
,fl
avon
oid
,
flav
on
ol
Mo
rin
(13
,44
)In
hib
ito
r
CY
P1
A1
Su
pp
lem
enta
ryd
rug
s
and
oth
ersu
bst
ance
s
Gra
pef
ruit
juic
esu
bst
ance
s,
flav
on
oid
,fl
avan
on
e
Nar
ing
enin
,le
ssp
ote
nt
inhib
ito
r(8
75
)In
hib
ito
r
CY
P1
A1
Su
pp
lem
enta
ryd
rug
s
and
oth
ersu
bst
ance
s
Nat
ura
lco
mp
ou
nd
,al
kal
oid
Nic
oti
ne
(63
5)
Ox
idat
ion
,C
50 -
(ox
idat
ion
to
coti
nin
e,at
hig
h
con
cen
trat
ion
)
Su
bst
rate
CY
P1
A1
Su
pp
lem
enta
ryd
rug
s
and
oth
ersu
bst
ance
s
Nat
ura
lco
mp
ou
nd
,
My
coto
xin
Och
rato
xin
A(2
39
,10
73
)H
yd
roxy
lati
on
,C
4-(
R)-
Su
bst
rate
RENDIC98
-
CY
P1
A1
Su
pp
lem
enta
ryd
rug
s
and
oth
ersu
bst
ance
s
Hal
luci
no
gen
ic(A
ng
eld
ust
,
An
gel
hai
r,A
ng
elm
ist,
etc.
),
anal
ges
ican
dan
esth
etic
Ph
ency
clid
ine
(46
6)
PC
HP
form
atio
n(m
ino
r
reac
tion)
Su
bst
rate
CY
P1
A1
Su
pp
lem
enta
ryd
rug
s
and
oth
ersu
bst
ance
s
Gra
pef
ruit
juic
esu
bst
ance
s,
flav
on
oid
,fl
avo
no
l;
P-g
lyco
pro
tein
(P-g
p)
inh
ibit
or/
acti
vat
or
Qu
erce
tin
(13
,44,8
44)
Inh
ibit
or
CY
P1
A1
Su
pp
lem
enta
ryd
rug
s
and
oth
ersu
bst
ance
s
Gra
pef
ruit
juic
esu
bst
ance
s,
flav
on
oid
,fl
avo
no
l;
P-g
lyco
pro
tein
(P-g
p)
inh
ibit
or/
acti
vat
or
Qu
erce
tin
(78
0)
Ind
uce
r
CY
P1
A1
Su
pp
lem
enta
ryd
rug
s
and
oth
ersu
bst
ance
s
Ph
yto
alex
in(i
nre
dw
ine,
gra
pe,
pea
nu
ts),
tra
ns-
Hyd
rox
yst
ilb
ene
der
ivat
ive,
cance
r
chem
op
rev
enti
ve
tran
s-R
esver
atro
l
(tra
ns-
3,4
0 ,5-t
rih
ydro
xy
stil
ben
e),
po
ten
t
inhib
ito
r(4
74
,68
6,8
75
,10
22
)
Inh
ibit
or
CY
P1
A1
Su
pp
lem
enta
ryd
rug
s
and
oth
ersu
bst
ance
s
Glu
tam
ate
anta
go
nis
t,u
sed
in
amyotr
ophic
late
ral
scle
rosi
s
Ril
uzo
le(5
24
)H
yd
roxy
lati
on
,N
-S