Lasofoxifene: A third-generation selective estrogen receptor modulator for the prevention and treatment of osteoporosis

Luigi Gennari, Daniela Merlotti, Giuseppe Martini, Ranuccio Nuti

Research output: Contribution to journalArticle

36 Citations (Scopus)

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 languageEnglish
Pages (from-to)1091-1103
Number of pages13
JournalExpert Opinion on Investigational Drugs
Volume15
Issue number9
DOIs
Publication statusPublished - Sep 2006

Fingerprint

Selective Estrogen Receptor Modulators
Osteoporosis
Postmenopausal Osteoporosis
Tamoxifen
Estrogen Receptors
Biological Availability
Estradiol
Therapeutics
Cholesterol
Safety
Bone and Bones
Lasofoxifene

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 journalArticle

Gennari, Luigi ; Merlotti, Daniela ; Martini, Giuseppe ; Nuti, Ranuccio. / Lasofoxifene : A third-generation selective estrogen receptor modulator for the prevention and treatment of osteoporosis. In: Expert Opinion on Investigational Drugs. 2006 ; Vol. 15, No. 9. pp. 1091-1103.
@article{f708f1d81e5248a5b00873a6e8f789b0,
title = "Lasofoxifene: A third-generation selective estrogen receptor modulator for the prevention and treatment of osteoporosis",
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.",
keywords = "Cholesterol, Estrogen receptor, Lasofoxifene, Osteoporosis, SERM",
author = "Luigi Gennari and Daniela Merlotti and Giuseppe Martini and Ranuccio Nuti",
year = "2006",
month = "9",
doi = "10.1517/13543784.15.9.1091",
language = "English",
volume = "15",
pages = "1091--1103",
journal = "Expert Opinion on Investigational Drugs",
issn = "1354-3784",
publisher = "Informa Healthcare",
number = "9",

}

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 -