Abstract
This article reviews lasofoxifene, a new-generation selective estrogen receptor modulator (SERM) that is currently in Phase III development for the prevention and treatment of osteoporosis in postmenopausal women. This compound selectively binds to both of the estrogen receptors with a high affinity and a median inhibitory concentration that is similar to that seen with estradiol and ≥ 10-fold higher than those reported for other SERMs (raloxifene and tamoxifen). Lasofoxifene has a remarkably improved oral bioavailability with respect to other SERMs due to increased resistance to intestinal wall glucuronidation. In both preclinical and short-term studies, the compound showed a favourable safety profile and demonstrated a proven efficacy in preventing bone loss and lowering cholesterol levels. Dose modelling from Phase II studies allowed the selection of lasofoxifene 0.25 mg/day as the lowest fully effective dose.
| Original language | English |
|---|---|
| Pages (from-to) | 1091-1103 |
| Number of pages | 13 |
| Journal | Expert Opinion on Investigational Drugs |
| Volume | 15 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - Sep 2006 |
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Keywords
- Cholesterol
- Estrogen receptor
- Lasofoxifene
- Osteoporosis
- SERM
ASJC Scopus subject areas
- Pharmacology
Cite this
Lasofoxifene : A third-generation selective estrogen receptor modulator for the prevention and treatment of osteoporosis. / Gennari, Luigi; Merlotti, Daniela; Martini, Giuseppe; Nuti, Ranuccio.
In: Expert Opinion on Investigational Drugs, Vol. 15, No. 9, 09.2006, p. 1091-1103.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Lasofoxifene
T2 - A third-generation selective estrogen receptor modulator for the prevention and treatment of osteoporosis
AU - Gennari, Luigi
AU - Merlotti, Daniela
AU - Martini, Giuseppe
AU - Nuti, Ranuccio
PY - 2006/9
Y1 - 2006/9
N2 - This article reviews lasofoxifene, a new-generation selective estrogen receptor modulator (SERM) that is currently in Phase III development for the prevention and treatment of osteoporosis in postmenopausal women. This compound selectively binds to both of the estrogen receptors with a high affinity and a median inhibitory concentration that is similar to that seen with estradiol and ≥ 10-fold higher than those reported for other SERMs (raloxifene and tamoxifen). Lasofoxifene has a remarkably improved oral bioavailability with respect to other SERMs due to increased resistance to intestinal wall glucuronidation. In both preclinical and short-term studies, the compound showed a favourable safety profile and demonstrated a proven efficacy in preventing bone loss and lowering cholesterol levels. Dose modelling from Phase II studies allowed the selection of lasofoxifene 0.25 mg/day as the lowest fully effective dose.
AB - This article reviews lasofoxifene, a new-generation selective estrogen receptor modulator (SERM) that is currently in Phase III development for the prevention and treatment of osteoporosis in postmenopausal women. This compound selectively binds to both of the estrogen receptors with a high affinity and a median inhibitory concentration that is similar to that seen with estradiol and ≥ 10-fold higher than those reported for other SERMs (raloxifene and tamoxifen). Lasofoxifene has a remarkably improved oral bioavailability with respect to other SERMs due to increased resistance to intestinal wall glucuronidation. In both preclinical and short-term studies, the compound showed a favourable safety profile and demonstrated a proven efficacy in preventing bone loss and lowering cholesterol levels. Dose modelling from Phase II studies allowed the selection of lasofoxifene 0.25 mg/day as the lowest fully effective dose.
KW - Cholesterol
KW - Estrogen receptor
KW - Lasofoxifene
KW - Osteoporosis
KW - SERM
UR - http://www.scopus.com/inward/record.url?scp=33748201643&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33748201643&partnerID=8YFLogxK
U2 - 10.1517/13543784.15.9.1091
DO - 10.1517/13543784.15.9.1091
M3 - Article
C2 - 16916275
AN - SCOPUS:33748201643
VL - 15
SP - 1091
EP - 1103
JO - Expert Opinion on Investigational Drugs
JF - Expert Opinion on Investigational Drugs
SN - 1354-3784
IS - 9
ER -