LASOFOXIFENE

Possibly Marketed Outside US

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C28H31NO2
Molecular Weight	413.5512
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

OC1=CC=C2[C@H]([C@H](CCC2=C1)C3=CC=CC=C3)C4=CC=C(OCCN5CCCC5)C=C4

InChI

InChIKey=GXESHMAMLJKROZ-IAPPQJPRSA-N

InChI=1S/C28H31NO2/c30-24-11-15-27-23(20-24)10-14-26(21-6-2-1-3-7-21)28(27)22-8-12-25(13-9-22)31-19-18-29-16-4-5-17-29/h1-3,6-9,11-13,15,20,26,28,30H,4-5,10,14,16-19H2/t26-,28+/m1/s1

HIDE SMILES / InChI

Molecular Formula	C28H31NO2
Molecular Weight	413.5512
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description

Lasofoxifene is an active component of Fablyn. Fablyn is used for the treatment of osteoporosis in postmenopausal women. Lasofoxifene is a nonsteroidal selective estrogen receptor modulator. Lasofoxifene has no effect on CYP2E1- or CYP2D6-mediated drug metabolism and should not affect drugs metabolized by other cytochrome P450 isoenzymes. Common adverse reactions considered to be related to Fablyn therapy were muscle spasms, hot flush and vaginal discharge. Lasofoxifene approved in the EU in 2009 is now withdrawn from use in the European Union.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Estrogen receptor alpha 127	Modulator 828		15.0 nM [IC50]
Estrogen receptor beta 110	Modulator 828

Conditions

Condition	Modality	Highest Phase	Product
Osteoporosis in postmenopausal women 6	Primary	Withdrawn	Fablyn
Advanced breast cancer 6	Primary	Phase III 656	Unknown
Female sexual dysfunction 5	Primary	Phase II 1,132	Unknown

C_max

Value	Dose	Analyte	Population
0.218 μg/mL	0.25 mg single, oral	LASOFOXIFENE plasma	Homo sapiens
0.09 ng/mL	0.01 mg 1 times / day steady-state, oral	LASOFOXIFENE plasma	Homo sapiens
0.25 ng/mL	0.03 mg 1 times / day steady-state, oral	LASOFOXIFENE plasma	Homo sapiens
0.74 ng/mL	0.1 mg 1 times / day steady-state, oral	LASOFOXIFENE plasma	Homo sapiens
2.08 ng/mL	0.3 mg 1 times / day steady-state, oral	LASOFOXIFENE plasma	Homo sapiens
6.43 ng/mL	1 mg 1 times / day steady-state, oral	LASOFOXIFENE plasma	Homo sapiens
0.169 ng/mL	0.25 mg single, oral	LASOFOXIFENE plasma	Homo sapiens
0.173 ng/mL	0.25 mg single, oral	LASOFOXIFENE plasma	Homo sapiens
0.214 ng/mL	0.25 mg single, oral	LASOFOXIFENE plasma	Homo sapiens
0.25 ng/mL	0.25 mg single, oral	LASOFOXIFENE plasma	Homo sapiens
0.5 ng/mL	0.5 mg single, oral	LASOFOXIFENE plasma	Homo sapiens
0.1 ng/mL	0.1 mg single, oral	LASOFOXIFENE plasma	Homo sapiens
0.24 ng/mL	0.25 mg single, oral	LASOFOXIFENE plasma	Homo sapiens
0.44 ng/mL	0.5 mg single, oral	LASOFOXIFENE plasma	Homo sapiens
0.09 ng/mL	0.1 mg single, oral	LASOFOXIFENE plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
52.7 ng × h/mL	0.25 mg single, oral	LASOFOXIFENE plasma	Homo sapiens
1.67 ng × h/mL	0.01 mg 1 times / day steady-state, oral	LASOFOXIFENE plasma	Homo sapiens
5.14 ng × h/mL	0.03 mg 1 times / day steady-state, oral	LASOFOXIFENE plasma	Homo sapiens
15.7 ng × h/mL	0.1 mg 1 times / day steady-state, oral	LASOFOXIFENE plasma	Homo sapiens
43.2 ng × h/mL	0.3 mg 1 times / day steady-state, oral	LASOFOXIFENE plasma	Homo sapiens
137 ng × h/mL	1 mg 1 times / day steady-state, oral	LASOFOXIFENE plasma	Homo sapiens
38.1 ng × h/mL	0.25 mg single, oral	LASOFOXIFENE plasma	Homo sapiens
37.1 ng × h/mL	0.25 mg single, oral	LASOFOXIFENE plasma	Homo sapiens
52.6 ng × h/mL	0.25 mg single, oral	LASOFOXIFENE plasma	Homo sapiens
45.8 ng × h/mL	0.25 mg single, oral	LASOFOXIFENE plasma	Homo sapiens
85.5 ng × h/mL	0.5 mg single, oral	LASOFOXIFENE plasma	Homo sapiens
14.5 ng × h/mL	0.1 mg single, oral	LASOFOXIFENE plasma	Homo sapiens
45.6 ng × h/mL	0.25 mg single, oral	LASOFOXIFENE plasma	Homo sapiens
77.5 ng × h/mL	0.5 mg single, oral	LASOFOXIFENE plasma	Homo sapiens
14.5 ng × h/mL	0.1 mg single, oral	LASOFOXIFENE plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
196 h	0.25 mg single, oral	LASOFOXIFENE plasma	Homo sapiens
182 h	0.03 mg 1 times / day steady-state, oral	LASOFOXIFENE plasma	Homo sapiens
171 h	0.1 mg 1 times / day steady-state, oral	LASOFOXIFENE plasma	Homo sapiens
147 h	0.3 mg 1 times / day steady-state, oral	LASOFOXIFENE plasma	Homo sapiens
134 h	1 mg 1 times / day steady-state, oral	LASOFOXIFENE plasma	Homo sapiens
193 h	0.25 mg single, oral	LASOFOXIFENE plasma	Homo sapiens
195 h	0.25 mg single, oral	LASOFOXIFENE plasma	Homo sapiens
252 h	0.25 mg single, oral	LASOFOXIFENE plasma	Homo sapiens
151.1 h	0.25 mg single, oral	LASOFOXIFENE plasma	Homo sapiens
134.8 h	0.5 mg single, oral	LASOFOXIFENE plasma	Homo sapiens
164.3 h	0.25 mg single, oral	LASOFOXIFENE plasma	Homo sapiens
146.3 h	0.5 mg single, oral	LASOFOXIFENE plasma	Homo sapiens

F_unbound

Value	Dose	Analyte	Population
0.508%	0.25 mg single, oral	LASOFOXIFENE plasma	Homo sapiens
0.717%	0.25 mg single, oral	LASOFOXIFENE plasma	Homo sapiens
0.433%	0.25 mg single, oral	LASOFOXIFENE plasma	Homo sapiens

Doses

Show entries

Dose	Population	Adverse events
1 mg 1 times / day steady-state, oral Highest studied dose	unhealthy, ADULT	Other AEs: Hot flushes, Leg cramps...
0.25 mg single, oral Studied dose	healthy, ADULT	Other AEs: somnolence, Headache...
0.25 mg 1 times / day steady-state, oral Studied dose	unhealthy, ADULT	Other AEs: Breast pain, Hot flushes...
20 mg single, oral Studied dose	healthy, ADULT

Showing 1 to 4 of 4 entries

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AEs

Show entries

AE	Significance	Dose	Population
Leg cramps	15 patients	1 mg 1 times / day steady-state, oral Highest studied dose	unhealthy, ADULT
Hot flushes	18 patients	1 mg 1 times / day steady-state, oral Highest studied dose	unhealthy, ADULT
Vaginal bleeding	2 patients	1 mg 1 times / day steady-state, oral Highest studied dose	unhealthy, ADULT
Leg cramps	2%	1 mg 1 times / day steady-state, oral Highest studied dose	unhealthy, ADULT
Fractures	5 patients	1 mg 1 times / day steady-state, oral Highest studied dose	unhealthy, ADULT

Showing 1 to 5 of 17 entries

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PubMed

Show entries

Title	Date	PubMed
Management of age-related osteoporosis and prevention of associated fractures.	2006 Sep	18360603
[Status of novel bone-targeting SERMs in development].	2007 Nov 28	18161145
Bazedoxifene: bazedoxifene acetate, TSE 424, TSE-424, WAY 140424.	2008	18457472
Effects of lasofoxifene on the uterus, vagina, and breast in ovariectomized cynomolgus monkeys (Macaca fascicularis).	2008 Aug	18501325
Bazedoxifene for the prevention of postmenopausal osteoporosis.	2008 Dec	19337430