Raloxifene: A Selective Estrogen Receptor Modulator (SERM) with Multiple Target System Effects

Muchmore, Douglas B.

doi:10.1634/theoncologist.5-5-388

Cited by 126 publications

(95 citation statements)

References 26 publications

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“…The drug belongs to a class of molecules known as selective estrogen receptor modulators (SERMs) and contains a benzothiophene heterocyclic moiety [2,3] , figure 1. During metabolism RLX undergoes a direct P450-mediated two-electron oxidation to form RLX diquinone methide.…”

Section: Introductionmentioning

confidence: 99%

Simulating the phase II metabolism of raloxifene on a screen-printed electrode

Vasiliadou

Welham

2017

Can. J. Chem.

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Raloxifene (RLX) is a selective estrogen receptor modulator widely used for the treatment of osteoporosis in post-menopause women. Toxicological in vitro studies suggested the reactivity of RLX through phase I metabolism. Herein, we describe a simple and inexpensive method for monitoring the reactive metabolism and detoxification of RLX by electrochemistry (EC) and mass spectrometry (MS). The phase I metabolite was synthesized electrochemically on a screenprinted electrode (SPE) and subsequently reacted with glutathione (GSH). The resulted GSHadducts and GSH disulfides were characterized off-line by electrospray ionization (ESI) /MS.3

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Section: Introductionmentioning

confidence: 99%

Simulating the phase II metabolism of raloxifene on a screen-printed electrode

Vasiliadou

Welham

2017

Can. J. Chem.

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“…Because of poor bioavailability, it is not able to reach uterus in sufficient amount to elicit the direct action on estrogen receptors. The non-specific distribution throughout the body causes various systemic side effects like hot flashes, sweating, headache, dizziness, spinning sensation, leg cramps, joint pain, nausea, vomiting, and stomach pain (Muchmore, 2000).…”

Section: Introductionmentioning

confidence: 99%

A gamma scintigraphy study to investigate uterine targeting efficiency of raloxifene-loaded liposomes administered intravaginally in New Zealand white female rabbits

et al. 2016

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Context: Raloxifene hydrochloride (RLH), a selective estrogen receptor modulator, shows antiproliferative and apoptotic effects on Leiomyoma. Its extensive first pass metabolism leads to oral bioavailability of 2%. Objective: The aim of this investigation was to formulate RLH-loaded liposomes and study its uterine-targeting efficiency after intravaginal administration. Materials and methods: Liposomes were prepared by thin film hydration method using 1:1 molar ratio of DSPC:Cholesterol and characterized for vesicle size, zeta potential, %entrapment efficiency, loading, drug release and transmission electron microscopy. Radiolabeling of RLH was performed with reduced technetium-99m ( 99m Tc). Binding affinity of 99m Tc-labeled complexes was assessed by diethylene triamine penta acetic acid (DTPA) challenge test. Biodistribution study was done in New Zealand white female rabbits by administering the formulation intravaginally. Results and discussion: Spherical and discrete liposomes of size 119 nm were seen in TEM results. Liposomes had high entrapment efficiency of 90.96% with drug loading of 27.25%w/w. Liposomes were able to sustain the drug release for 6 days. Tc-labeled complexes showed high labeling efficiency and stability both in saline and serum. DTPA challenge test confirmed low transchelation of 99m Tc-labeled complexes. Biodistribution study by gamma scintigraphy revealed the preferential uptake of the formulation by uterus when administered vaginally. Compared to plain drug, liposomes were concentrated and retained within the uterus for a longer period of time. Conclusion: Uterine targeting of RLH-loaded liposomes indicates its potential to overcome the limitations of marketed formulation. Drug targeting to site of action anticipates dose reduction needed to elicit the therapeutic effect.

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“…Raloxifene hydrochloride is a Selective estrogen receptor modulator that produces estrogen-agonistic effects on bone and lipid metabolism and hence is used in treatment and prevention of postmenopausal osteoporosis 1 . Currently Raloxifene is available in tablet form only; but on oral administration it undergoes extensive first pass metabolism to hepatic glucuronide conjugates.…”

Section: Introductionmentioning

confidence: 99%

Untitled

2010

IJPSR

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The present investigation was taken up to prepare and evaluate a transdermal drug delivery system (patch) of Raloxifene Hydrochloride to increase its bioavailability. The matrix type patches were prepared using different ratios of Eudragit RL100, Poly vinyl Pyrrolidone K-30, HPMC, CAP and PEG6000 in different ratios. All the prepared formulations were subjected to physical studies (weight variation, thickness, moisture content, moisture uptake, flatness, Water Vapour transmission rate, folding endurance, tensile strength, and % elongation), thumb tack test, in vitro release studies, and in vitro diffusion studies. In vitro permeation studies were performed using artificial membrane and across skin derived from albino rat. The accelerated stability studies for the formulations were performed as per the ICH guidelines. The studies showed that formulation prepared with HPMC and CAP in ratio 5:2 with adhesive polyisobutylene and Eudragit RL100 & PVP in ratio 6:4 (self sticking) were the effective systems to achieve desired results. The interaction studies carried out by comparing the results of TLC, Infrared and UV analysis of pure drug and medicated patches indicated no chemical interaction between drug and excipients.

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Raloxifene: A Selective Estrogen Receptor Modulator (SERM) with Multiple Target System Effects

Cited by 126 publications

References 26 publications

Simulating the phase II metabolism of raloxifene on a screen-printed electrode

Simulating the phase II metabolism of raloxifene on a screen-printed electrode

A gamma scintigraphy study to investigate uterine targeting efficiency of raloxifene-loaded liposomes administered intravaginally in New Zealand white female rabbits

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