2-(4-(4-chloro-1,2-diphenyl-but-1-enyl)phenoxy)ethanol

Absorption

When a single oral dose of ospemifene 60 mg is given to postmenopausal women under fasted conditions, the pharmacokinetic parameters are as follows: Tmax = 2 hours (range of 1 - 8 hours); Cmax = 533 ng/mL; AUC (0-inf) = 4165 ng?hr/mL. When the same aforementioned dose is given to postmenopausal women under fed conditions, the pharmacokinetic parameters are as follows: Tmax = 2.5 hours (1 - 6 hours); Cmax = 1198 ng/mL; AUC (0-inf) = 7521 ng?hr/mL. Accumulation occurs following repeated doses. Time to steady state = 9 days. Although the bioavailability of ospemifene has not been formally evaluated, it is expected to have a low bioavailability because of its lipophilic nature.

Toxicity

Adverse reactions (≥1 percent) include: hot flush, vaginal discharge, muscle spasms, genital discharge, hyperhidrosis.

Description

In February 2013, the US FDA approved ospemifene (also referred to as FC1271a), for the treatment ofmoderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy (VVA), due tomenopause. It is estimated that there are 150 million postmenopausal women worldwide with 40–70% suffering from VVA. Ospemifene is a selective estrogen receptor (ER) modulator (SERM) and the first nonhormonal, nonestrogen for the treatment of moderate to severe dyspareunia in women with menopausal VVA. It binds to ERα (IC₅₀～800 nM) and ERβ (IC₅₀～1600 nM) with tissue-specific estrogenic agonist/antagonist effects. Treatment with ospemifene increases the thickness of the vaginal tissue thereby decreasing fragility of the tissue and reducing potential for pain during sexual intercourse.

The Uses of 2-(4-(4-chloro-1,2-diphenyl-but-1-enyl)phenoxy)ethanol

Treatment of vaginal atrophy, osteoporosis, and vasomotor symptoms.

Indications

Ospemifene is indicated for the treatment of moderate to severe dyspareunia and vaginal dryness associated with menopause.

Background

Ospemifene is a new selective non-hormonal estrogen receptor modulator (SERM) that is used for the treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause. FDA approved on February 26, 2013.

Pharmacokinetics

The half maximal inhibitory concentration (IC50) for estrogen receptor (ER) alpha and beta are 0.8 μM and 1.7 μM, respectively. Ospemifene has potential uses in the management of osteoporosis in postmenopausal women. It interacts with osteoblasts and osteoclasts in such a way that it reduces bone turnover. It also has potential uses in the prevention of breast cancer. Studies suggest that ospemifene, in a dose-dependent manner, reduces the incidence of tumours.

Metabolism

Ospemifene is hepatically metabolized via CYP3A4, CYP2C9, CYP2C19, and CYP2B6. The major metabolite was 4-hydroxyospemifene, 25% of the parent compound will undergo this biotransformation. Other metabolites include 4'-hydroxy-ospemifene, <7% of the parent compound will undergo this biotransformation. In order of decreasing potency, ospemifene was suggested to be a weak inhibitor for CYP2B6, CYP2C9, CYP2C19, CYP2C8, CYP2D6 and CYP3A4.