Bexarotene

In this article, we will discuss Bexarotene (Mechanism of Action). So, let’s get started.

Bexarotene selectively binds and activates retinoid X receptor subtypes (RXRα, RXRβ, RXRγ). RXRs can form heterodimers with various receptor partners such as retinoic acid receptors (RARs), vitamin D 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. The exact mechanism of action of bexarotene in the treatment of cutaneous T-cell lymphoma (CTCL) is unknown.

Pharmacokinetics

Absorption

After oral administration of Targretin capsules, bexarotene is absorbed with a Tmax of about two hours. Terminal half-life of bexarotene is about seven hours. Studies in patients with advanced malignancies show approximate single dose linearity within the therapeutic range and low accumulation with multiple doses. Plasma bexarotene AUC and Cmax values resulting from a 75 to 300 mg dose were 35% and 48% higher, respectively, after a fat-containing meal than after a glucose solution.

Distribution

Bexarotene is highly bound (>99%) to plasma proteins. The plasma proteins to which bexarotene binds have not been elucidated, and the ability of bexarotene to displace drugs bound to plasma proteins and the ability of drugs to displace bexarotene binding have not been studied. The uptake of bexarotene by organs or tissues has not been evaluated.

Metabolism

Four bexarotene metabolites have been identified in plasma: 6- and 7-hydroxy-bexarotene and 6- and 7-oxo-bexarotene. In vitro studies suggest that cytochrome P450 3A4 is the major cytochrome P450 responsible for formation of the oxidative metabolites and that the oxidative metabolites may be glucuronidated. The oxidative metabolites are active in in vitro assays of retinoid receptor activation, but the relative contribution of the parent and any metabolites to the efficacy and safety of Targretin capsules is unknown.

Elimination

The renal elimination of bexarotene and its metabolites was examined in patients with Type 2 diabetes mellitus. Neither bexarotene nor its metabolites were excreted in urine in appreciable amounts. Bexarotene is thought to be eliminated primarily through the hepatobiliary system

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