Search References Drug Actions/Targets About Access data Feedback
Sign In
mitontu@gmail.com
2021 MitoTox | (CC BY-NC 4.0)
Drug

D1081 | raloxifene

Molecular Formula C28H27NO4S
Molecular Weight 473.6
Structure
State solid
Clearance Following intravenous administration, raloxifene was shown to be cleared at a rate approximating hepatic blood flow. The apparent oral clearance is reported to be 44.1 L/kgxhr. The clearance can range from 40 to 60L/kgxhr following chronic dosing. In healthy postmenopausal women receiving multiple oral dose, the mean clearance was 47.4 L/kgxhr. Apparent clearance can be reduced by 56% in patients with hepatic impairment.[label]
Volume of distribution Following oral administration of single doses randing from 30 to 150 mg in postmenopausal women, the volume of distribution was about 2348 L/kg. Following oral administration of multiple doses, the value increased to 2853 L/kg. Raloxifene is widely distributed in the tissues. It is not known whether raloxifene is excreted in human milk.[label]
Route of elimination Raloxifene predominantly undergoes fecal excretion, with less than 0.2% of the dose being excreted in the urine as unchanged form of the compound and less than 6% of the dose being excreted as glucuronide conjugates. Co-administration with [cholestyramine], a bile acid sequestrant, was shown to reduce the enterohepatic recycling of raloxifene by 60%.[T28]
Protein binding About 95% of raloxifene and its glucuronide metabolites are bound to plasma proteins.[label] Although this is a relatively high protein binding profile, _in vitro_ studies suggest that raloxifene and its metabolites do not significantly interact with binding of highly protein-bound drugs.[A4977] FDA Label still advises patients to use raloxifene with caution co-administering with other highly protein-bound drugs.[label]
Half life The average plasma elimination half-life of raloxifene ranges from 27 to 32 hours.[A4977,T28] The prolonged half-life has been attributed to the drug's reversible systemic metabolism and significant enterohepatic cycling.[A4977]
Absorption Raloxifene is well absorbed from the gastrointestinal tract, with approximately 60% fo the drug being absorbed following oral administration.[T28] Due to the extensive first-pass hepatic metabolism that involves glucuronide conjugation, the absolute oral bioavailability of raloxifene is about 2%.[T28] Following oral ingestion of a single dose or multiple dose of raloxifen in healthy postmenopausal women, the mean peak plasma concentrations (Cmax) were 0.50 and 1.36 ng/mL, respectively, and the AUC values were 27.2 and 24.2 ngxhr/mL, respectively. The time to reach Cmax following a single or multiple oral doses were 27.7 and 32.5 hours, respectively.[label] Although not clinically significant, oral ingestion of raloxifene with high-fat meals is thought to increase the systemic bioavailability of the drug[A4977] by increasnig the peak plasma concentrations (Cmax) and AUC by 28% and 16%, respectively.[label]

G

G03XC01 Raloxifene


[G03XC] Selective estrogen receptor modulators


[G03X] OTHER SEX HORMONES AND MODULATORS OF THE GENITAL SYSTEM


[G03] SEX HORMONES AND MODULATORS OF THE GENITAL SYSTEM


[G] Genitourinary system and reproductive hormones

Toxicity Dose Time Species Model Method Action Positive criterion Reference
MEMBRANE POTENTIAL 5.05±3.99 human qHTS-HepG2 MMP assay decrease IC50 163
MEMBRANE POTENTIAL 17.78 human HepG2 MMP assay decrease IC50 163
MEMBRANE POTENTIAL 22.40±24.05 rat hepatocytes MMP assay decrease IC50 163

Pictogram Signal Statements Precautionary Statement Codes
Warning

The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.


H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]


H315 (100%): Causes skin irritation [Warning Skin corrosion/irritation]


H319 (100%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]


H332 (100%): Harmful if inhaled [Warning Acute toxicity, inhalation]


H335 (100%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure


Respiratory tract irritation]


 P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P312, P304+P340, P305+P351+P338, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, and P501; (The corresponding statement to each P-code can be found at the GHS Classification page.)

Organism Test type Route Dose (normalized dose) Effect Source
women TDLo oral 36mg/kg/30D-I (36mg/kg) Lancet. Vol. 352, Pg. 1524, 1998.


  • (2-(4-Hydroxyphenyl)-6-hydroxybenzo(b)thien-3-yl)(4-(2-(1-piperidinyl)ethoxy)phenyl)methanone (6-hydroxy-2-(4-hydroxyphenyl)benzo[b]thiophen-3-yl)(4-(2-(piperidin-1-yl)ethoxy)phenyl)methanone 15189-EP2270008A1
    15189-EP2272825A2 15189-EP2280012A2 15189-EP2281815A1
    15189-EP2289892A1 15189-EP2292615A1 15189-EP2292617A1
    15189-EP2295426A1 15189-EP2295427A1 15189-EP2301928A1
    15189-EP2301933A1 15189-EP2305640A2 15189-EP2305671A1
    15189-EP2308855A1 15189-EP2311808A1 15189-EP2311825A1
    15189-EP2311827A1 15189-EP2311829A1 15189-EP2311840A1
    15189-EP2311842A2 15189-EP2314581A1 15189-EP2316832A1
    15189-EP2316833A1 2-(4-hydroxyphenyl)-3-({4-[2-(piperidin-1-yl)ethoxy]phenyl}carbonyl)-1-benzothiophen-6-ol 2-(4-hydroxyphenyl)-3-{4-[2-(piperidin-1-yl)ethoxy]benzoyl}-1-benzothiophen-6-ol
    449R901 6-Hydroxy-2-(4-Hydroxyphenyl)-3-[4(2-Piperidinoethoxy)benzoyl]benzo[b]thiophene 6-hydroxy-2-(4-hydoxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo[b]thiophene
    6-hydroxy-2-(4-hydoxyphenyl)-3[-4-(2-piperidinoethoxy)benzoyl]benzo[b]thiophene 6-hydroxy-2-(4-hydroxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo[b]-thiophene 6-hydroxy-2-(4-hydroxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo[b]thiophene
    6-hydroxy-2-(4-hydroxyphenyl)-3-[4-(2piperidinoethoxy)-benzoyl]benzo[b]thiophene 6-hydroxy-2-(4-hydroxyphenyl)-3[-4-(2-piperidinoethoxy)benzoyl]benzo [b]thiophene 6-hydroxy-2-(4-hydroxyphenyl)-3[-4-(2-piperidinoethoxy)benzoyl]benzo[b]thiophene
    6-hydroxy-2-(4-hydroxyphenyl)-3[-4-(2piperidinoethoxy)benzoyl]benzo[b]thiophene 6-hydroxy-2-(4-hydroxyphenyl)benzo[b]thien-3-yl 4-[2-(1-piperidinyl)ethoxy]phenyl methanone; 6-hydroxy-2-(4-hyroxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo[b]thiophene
    84449-90-1 AB0073011 AC-8399
    AKOS015896267 API0003075 AS-35086
    BCP09772 BDBM19441 BIDD:ER0216
    BIDD:GT0795 BPBio1_000995 BRD-K63828191-003-11-5
    BSPBio_000903 C-22734 C07228
    C28H27NO4S CAS-82640-04-8 CAS-84449-90-1
    CC-34210 CCG-205128 CCRIS 7129
    CHEBI:8772 CHEMBL81 D08465
    DB00481 DSSTox_CID_3550 DSSTox_GSID_23550
    DSSTox_RID_77076 DTXSID3023550 Eviden (TN)
    FT-0630926 GTPL2820 GZUITABIAKMVPG-UHFFFAOYSA-N
    HMS2089F06 HMS3742O11 HSDB 7460
    J22.982B KBio2_002361 KBio2_004929
    KBio2_007497 KBio3_002840 KBioGR_002361
    KBioSS_002364 Keoxifene LS-177821
    LY 139481 LY-139481 LY-156758
    LY139481 Lopac-R-1402 Lopac0_001051
    MCULE-4598311006 MRF-0000684 Methanone, (6-hydroxy-2-(4-hydroxyphenyl)benzo(b)thien-3-yl)(4-(2-(1-piperidinyl)ethoxy)phenyl)-
    Methanone, [6-Hydroxy-2-(4-hydroxyphenyl)benzo[b]thien-3-yl][4-[2-(1-piperidinyl)ethoxy]phenyl]- NCGC00015889-01 NCGC00015889-02
    NCGC00015889-04 NCGC00015889-05 NCGC00015889-06
    NCGC00015889-07 NCGC00015889-08 NCGC00015889-10
    NCGC00092353-02 NCGC00092353-04 NCGC00260151-01
    NSC-747974 NSC747974 Optruma
    Pharoxifene Prestwick0_000862 Prestwick1_000862
    Prestwick2_000862 Prestwick3_000862 Q425223
    RAL Raloxifene (INN) Raloxifene [INN:BAN]
    Raloxifene, 6 Raloxifeno Raloxifeno [Spanish]
    Raloxifenum Raloxifenum [Latin] Raxeto (TN)
    SBI-0051021.P002 SC-17311 SCHEMBL6144
    SMP2_000095 SPBio_002824 Tox21_202603
    UNII-YX9162EO3I VU0155042-3 YX9162EO3I
    ZINC538275 [2-(4-Hydroxyphenyl)-6-hydroxybenzo[b]thien-3-yl][4-(2-(1-piperidinyl)ethoxy)phenyl]methanone [2-(4-hydroxyphenyl)-6-hydroxybenzo[b]thien-3-yl][4-[2-(1-piperidinyl)ethoxy]phenyl]methanone
    [6-Hydroxy-2-(4-hydroxy-phenyl)-benzo[b]thiophen-3-yl]-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanone [6-hydroxy-2-(4-hydroxyphenyl)-1-benzothien-3-yl][4-(2-piperidin-1-ylethoxy)phenyl]methanone [6-hydroxy-2-(4-hydroxyphenyl)-1-benzothien-3-yl]{4-[(2-piperidin-1-ylethyl)oxy]phenyl}methanone
    [6-hydroxy-2-(4-hydroxyphenyl)-1-benzothiophen-3-yl]-[4-(2-piperidin-1-ylethoxy)phenyl]methanone [6-hydroxy-2-(4-hydroxyphenyl)-1-benzothiophen-3-yl][4-(2-piperidin-1-ylethoxy)phenyl]methanone [6-hydroxy-2-(4-hydroxyphenyl)benzo-[b]thien-3-yl][4-[2-(1-piperidinyl)ethoxy]phenyl]methanone
    [6-hydroxy-2-(4-hydroxyphenyl)benzo[b]thien-3-yl]-[4-[2-(1-piperidinyl)ethoxy]phenyl]methanone [6-hydroxy-2-(4-hydroxyphenyl)benzo[b]thien-3-yl]-[4-[2-(1piperidinyl)ethoxy]phenyl]methanone [6-hydroxy-2-(4-hydroxyphenyl)benzo[b]thien-3-yl][4-[2-(1-piperidinyl)ethoxy]phenyl]methanone
    [6-hydroxy-2-(4-hydroxyphenyl)benzothiophen-3-yl]-[4-[2-(1-piperidyl)ethoxy]phenyl]methanone cMAP_000032 cid_11071264
    raloxifene s5781

    DrugBank DB00481
    CAS Number 1020061-04-4, 82640-04-8, 84449-90-1
    PubChem Compound 5035
    KEGG Compound ID C07228
    KEGG Drug D08465
    ChEBI 8772
    PharmGKB PA451221