Dexamethasone phosphate  (Synonyms: Dexamethasone 21-phosphate)

Dexamethasone phosphate (Dexamethasone 21-phosphate) is a prodrug form of the glucocorticoid Dexamethasone (HY-14648). Dexamethasone phosphate is prepared by introducing a phosphate ester group to the hydroxyl group at position 21 of the Dexamethasone molecule. Dexamethasone phosphate inhibits LPS (HY-D1056)-induced degradation of IRAK-1 and IRAK-4, and blocks LPS-induced activation of TRAF6, p-TAK1 and p-JNK. Dexamethasone phosphate inhibits the secretion of RANTES, TGF-β1 and NO, promotes the production of MIP-1α and IL-10, and blocks microglial migration. Dexamethasone phosphate is almost completely converted to Dexamethasone in rat blood, and supports transdermal delivery via iontophoresis. Dexamethasone phosphate can be used in research related to steroid-dependent ulcerative colitis, chemotherapy-induced vomiting, allergic asthma and acute colitis (inflammatory bowel disease)^{[1][2][3][4][5][6]}.

Dexamethasone phosphate (1, 2, 4 μM; 23 h) does not induce cytotoxicity in BV-2 microglial cells^[1].
Dexamethasone phosphate (1, 2, 4 μM; 3 h pre-incubation, followed by 24 h LPS co-incubation) dampens LPS-induced secretion of RANTES, TGF-β1, and NO in BV-2 microglial cells, while dexamethasone phosphate (4 μM; 24 h incubation alone) has no inhibitory effect on these mediators^[1].
Dexamethasone phosphate (4 μM; 3 h pre-incubation, followed by 24 h LPS co-incubation) increases LPS-reduced production of IL-10 and MIP-1α in BV-2 microglial cells, while dexamethasone phosphate (4 μM; 24 h incubation alone) reduces IL-10 production in untreated BV-2 microglial cells^[1].
Dexamethasone phosphate (4 μM; 3 h pre-incubation in lower chambers, followed by 18 h LPS co-incubation) mitigates LPS-induced migration of BV-2 microglial cells, while having no effect on migration of untreated BV-2 microglial cells when used at 4 μM for 18 h incubation alone^[1].
Dexamethasone phosphate (1, 2, 4 μM; 3 h pre-incubation, followed by 30 min LPS co-incubation) ameliorates LPS-induced degradation of IRAK-1 and IRAK-4, and inhibits LPS-induced activation of TRAF6, p-TAK1, and p-JNK in BV-2 microglial cells^[1].
Dexamethasone phosphate (5×10^-6 M; 5-min intervals at 37°C) undergoes hydrolysis to Dexamethasone free alcohol in human whole blood in vitro with a first-order rate constant of 0.162 hr^-1, which is 25-fold slower than its in vivo conversion rate^[3].
Dexamethasone phosphate (200 μM; 7 h) shows good stability with limited hydrolysis when incubated with human, porcine, or rat dermis for 7 hours, with 72.5-82.2% of the prodrug remaining intact^[4].
Dexamethasone phosphate (50.8-51.8% drug loading; heated at 20 °C min^-1) intercalated into MgAl layered double hydroxides enhances the thermal stability of dexamethasone phosphate disodium, with its decomposition occurring at temperatures higher than those of free sexamethasone phosphate disodium^[5].
Dexamethasone phosphate (50.8-51.8% drug loading) is successfully intercalated into MgAl layered double hydroxides via electrostatic interactions, with no denaturation of the drug molecules, as confirmed by preserved characteristic FT-IR bands and shifted phosphate group vibrations^[5].
Dexamethasone phosphate (1.5 mg/mL; 50 hours) is efficiently encapsulated by the NPA₂ coacervate, which mediates sustained release of the drug over 50 hours in a cell-free in vitro system^[6].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Dexamethasone phosphate (40 mM; iontophoresis; 0.5 mA cm^-2; 5 hours) administered via cathodal iontophoresis in male Wistar rats achieves rapid, significant systemic Dexamethasone levels^[4].
Dexamethasone phosphate (0.25 mg/kg; i.p.; daily; 8 days) reduces inflammatory cell counts, Th2 cytokine levels, airway hyperresponsiveness, and lung tissue inflammation in ovalbumin-induced asthmatic Sprague-Dawley rats^[5].
Dexamethasone phosphate (1.15 mg per dose; p.o.; on days 1, 3, and 5) via Dexamethasone phosphate coacervate significantly reduces acute colitis severity (mean histopathology score 0.500), restores gut barrier function and microbiota diversity, and lowers systemic drug exposure compared to equivalent Dex-P aqueous solution treatment^[6].
Dexamethasone phosphate (~1.15 mg; p.o.; single administration) via NPA₂ coacervate sustains serum Dexamethasone levels at a lower therapeutic range for over 40 h in healthy rats, reducing systemic drug exposure compared to Dexamethasone phosphate aqueous solution^[6].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

472.44

C₂₂H₃₀FO₈P

312-93-6

Solid

White to off-white

O=C1C=C[C@@]2(C)C(CC[C@]3([H])[C@]2(F)[C@@H](O)C[C@@]4(C)[C@@]3([H])C[C@@H](C)[C@]4(O)C(COP(O)(O)=O)=O)=C1

Room temperature in continental US; may vary elsewhere.

-20°C, stored under nitrogen

*In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

• [1]. Hui B, et al. Dexamethasone sodium phosphate attenuates lipopolysaccharide-induced neuroinflammation in microglia BV2 cells. Naunyn Schmiedebergs Arch Pharmacol. 2020;393(9):1761-1768.

  [2]. Bossa F, et al. Erythrocytes-mediated delivery of dexamethasone 21-phosphate in steroid-dependent ulcerative colitis: a randomized, double-blind Sham-controlled study. Inflamm Bowel Dis. 2013;19(9):1872-1879.  [Content Brief]

  [3]. Hare LE, et al. Bioavailability of dexamethasone. II. Dexamethasone phosphate. Clin Pharmacol Ther. 1975 Sep;18(3):330-7.

  [4]. Cázares-Delgadillo J, et al. Transdermal iontophoresis of dexamethasone sodium phosphate in vitro and in vivo: effect of experimental parameters and skin type on drug stability and transport kinetics. Eur J Pharm Biopharm. 2010;75(2):173-178.

  [5]. Wen-Rui Wang, et al. Dexamethasone sodium phosphate intercalated layered double hydroxides and their therapeutic efficacy in a murine asthma model. RSC Adv., 2015, 5, 23826-23834.

  [6]. Zhao P, et al. Nanoparticle-assembled bioadhesive coacervate coating with prolonged gastrointestinal retention for inflammatory bowel disease therapy. Nat Commun. 2021;12(1):7162. Published 2021 Dec 9.  [Content Brief]