Targretin: profile and news

Ligand Announces Financial Results for First Quarter of Fiscal ... May 15, 2006
...same period in 2005 reflects a 48% increase of AVINZA(R) net sales to $32.5 million and, as expected, strong oncology sales growth led by Targretin(R) capsules ... - Genetic Engineering News,

Other information

Indication
For the treatment of cutaneous manifestations of cutaneous T-cell lymphoma in patients who are refractory to at least one prior systemic therapy

Pharmacology
Bexarotene is a member of a subclass of retinoids that selectively activate retinoid X receptors (RXRs). These retinoid receptors have biologic activity distinct from that of retinoic acid receptors (RARs). Bexarotene is indicated for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma in patients who are refractory to at least one prior systemic therapy. Bexarotene selectively binds and activates retinoid X receptor subtypes (RXR_a, RXR_b, RXR_g). RXRs can form heterodimers with various receptor partners such as retinoic acid receptors (RARs), vitamin Dy receptor, thyroid receptor, and peroxisome proliferator activator receptors (PPARs). Once activated, these receptors function as transcription factors that regulate the expression of genes that control cellular differentiation and proliferation. Bexarotene inhibits the growth in vitro of some tumor cell lines of hematopoietic and squamous cell origin. It also induces tumor regression in vivo in some animal models.

Mechanism Of Action
The exact mechanism of action of bexarotene in the treatment of cutaneous T-cell lymphoma (CTCL) is unknown.

Drug Category
Anticarcinogenic Agents; ATC:L01XX25

Brand Names/Synonyms
Bexarotene; Bexarotene [Usan]; LG 1069; LG 69; LGD 1069; LGD1096; Targret; Targretin; Targretyn; Targrexin

Dosage Forms
Not Available

Absorption
Not Available

Interactions
Interactions for Bexarotene:

No formal studies to evaluate drug interactions with bexarotene have been conducted. Bexarotene oxidative metabolites appear to be formed by cytochrome P450 3A4.

On the basis of the metabolism of bexarotene by cytochrome P450 3A4, ketoconazole, itraconazole, erythromycin, gemfibrozil, grapefruit juice, and other inhibitors of cytochrome P450 3A4 would be expected to lead to an increase in plasma bexarotene concentrations. Furthermore, rifampin, phenytoin, phenobarbital, and other inducers of cytochrome P450 3A4 may cause a reduction in plasma bexarotene concentrations.

Concomitant administration of Targretin ® capsules and gemfibrozil resulted in substantial increases in plasma concentrations of bexarotene, probably at least partially related to cytochrome P450 3A4 inhibition by gemfibrozil. Under similar conditions, bexarotene concentrations were not affected by concomitant atorvastatin administration. Concomitant administration of gemfibrozil with Targretin ® capsules is not recommended.

Chemical IUPAC Name
4-[1-(3,5,5,8,8-pentamethyltetralin-2-yl)ethenyl]benzoicacid

Chemical Formula
C24H28O2

Half Life
7 hours

Drug Type
Approved Drug

# Accession No
APRD00114

CAS Registry Number
153559-49-0