Ocular PK: After topical instillation of 1% hydrocortisone sodium phosphate eye drops (50 μL) in cataract patients, aqueous humor concentrations peaked at 30 min (Tₘₐₓ) with Cₘₐₓ = 23.8 ng/mL. AUC₀₋₁₂₀ was 1342 ng·min/mL. Elimination half-life = 46 min. Systemic absorption was negligible (plasma concentrations below detection limit).[1]
In rats with acetic acid-induced stomach ulcers, hydrocortisone sodium phosphate (2.5 mg/kg, intraperitoneal injection, daily) can postpone the healing process [2].

Animal/Disease Models: Wistar rat [2]
Doses: 2.5 mg/kg
Route of Administration: 2.5 mg/kg, intraperitoneal (ip) injection, daily
Experimental Results: Caused significant delay in healing of acetic acid-induced ulcers.

Ocular pharmacokinetics: After topical administration of 1% hydrocortisone sodium phosphate eye drops (50 μL) to cataract patients, the aqueous humor concentration reached its peak at 30 minutes (Tₘₐₓ), Cₘₐₓ = 23.8 ng/mL. The AUC₀₋₁₂₀ was 1342 ng·min/mL. The elimination half-life was 46 minutes. Systemic absorption was negligible (plasma concentration was below the detection limit). [1]

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The pharmacokinetic properties of hydrocortisone phosphate are characterized by its role as a water-soluble prodrug of hydrocortisone. Key PK parameters include:
Absorption: Following intravenous administration, hydrocortisone phosphate is rapidly hydrolyzed to free hydrocortisone by plasma phosphatases. After topical ocular administration of 0.33% hydrocortisone sodium phosphate eye drops, peak hydrocortisone concentration in the aqueous humor reaches approximately 35.2 ± 20.2 ng/mL, with peak penetration observed 60-120 minutes post-instillation. The steroid persists at relatively stable concentrations until around 150 minutes, followed by a slow decline.
Hydrolysis and Activation: As a phosphate ester prodrug, hydrocortisone phosphate requires enzymatic hydrolysis to release the active parent drug. Stability studies have shown that the compound is susceptible to pH-dependent hydrolysis and may degrade during iontophoretic drug delivery if not properly buffered.
Plasma Protein Binding: After conversion to hydrocortisone, the drug is highly protein-bound (>90%), primarily to corticosteroid-binding globulin (CBG) and albumin.
Distribution: Free (unbound) hydrocortisone distributes into the extracellular space and can be sampled by microdialysis. The unbound fraction fluctuates rapidly in vivo, with changes observed between 2-minute sampling intervals.
Elimination Half-life: After intravenous administration in rats, unbound hydrocortisone decreases to predose endogenous concentrations in a first-order fashion with a half-life of 17-29 minutes.
Special Considerations: In primates, chronic administration of hydrocortisone phosphate (5-15 mg/day for 1-2 menstrual cycles) results in sustained serum cortisol elevation followed by prolonged HPA axis suppression after therapy cessation, with cortisol levels remaining below baseline for at least one subsequent menstrual cycle.

In rats with acetic acid-induced gastric ulcers, subcutaneous injection of hydrocortisone sodium phosphate (50 mg/kg/day) significantly delayed ulcer healing: the ulcer index increased to 129 ± 11, compared to 59 ± 7 in the control group (p<0.01). This resulted in severe mucosal damage, accompanied by neutrophil infiltration and edema. Body weight gain was reduced by 12% compared to the control group. [2]

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441406 Rats Oral LD50 6100 mg/kg Gekkan Yakuji. Pharmaceuticals Monthly., 21(2117), 1979
441406 Rats Intraperitoneal LD50 603 mg/kg Behavior: Somnolence (overall activity inhibition); Behavioral: Seizures or influence on seizure threshold; Behavioral: Ataxia Yakkyoku. Pharmacy., 26(379), 1975
441406 Rats Subcutaneous LD50 680 mg/kg Gekkan Yakuji. Pharmaceuticals Monthly., 21(2117), 1979
441406 Rats Intravenous LD50 632 mg/kg Behavioral studies: somnolence (overall activity inhibition); behavioral studies: seizures or influence on seizure threshold; behavioral studies: ataxia. Yakkyoku. Pharmacy, 26(379), 1975. 441406 Rat intramuscular injection LD50 1500 mg/kg. Monthly Pharmacy, 21(2117), 1979.

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The toxicological profile of hydrocortisone phosphate has been evaluated through clinical use and case reports:
Hypersensitivity Reactions: A documented case report describes a 62-year-old male patient who experienced a severe asthmatic attack approximately 5 minutes after intravenous administration of 200 mg Hydrocortone Phosphate Injection. Provocation challenge testing with 100 mg of the drug produced dramatic confirmation of the reaction. Interestingly, the patient showed no adverse reactions to other corticosteroid products including Solu-Cortef (hydrocortisone hemisuccinate), dexamethasone phosphate, prednisolone phosphate, prednisolone hemisuccinate, oral hydrocortisone, or oral methylprednisolone. Skin tests to crude hydrocortisone phosphate were negative, but skin tests to diluents were idiosyncratically positive. Passive cutaneous anaphylaxis testing in Japanese monkey skin showed positive results for hydrocortisone phosphate but negative for the diluent, suggesting that the reaction may be specific to the phosphate ester or a unique hypersensitivity mechanism.
Endocrine Toxicity: Subchronic administration of hydrocortisone phosphate in primates (5-15 mg/day for 1-2 menstrual cycles) results in sustained suppression of adrenal androgens to 0.4-0.6 of baseline levels, with prolonged HPA axis suppression persisting after treatment cessation. Serum cortisol remained suppressed to 0.6-0.8 of baseline in the cycle following treatment.
HPA Axis Suppression: As with all systemic glucocorticoids, prolonged or high-dose use of hydrocortisone phosphate can cause hypothalamic-pituitary-adrenal (HPA) axis suppression, leading to adrenal insufficiency upon drug withdrawal.
Ocular Side Effects: Topical ophthalmic use of hydrocortisone requires consideration of the lowest clinically effective dose to minimize steroid exposure in the anterior chamber and avoid side effects including intraocular pressure increase and cataract development.
Drug Stability and Degradation: Hydrocortisone phosphate is susceptible to pH-dependent hydrolysis during administration (e.g., during iontophoresis), and degradation products may have unknown toxicity profiles.

[1]. Kinetics of hydrocortisone sodium phosphate penetration into the human aqueous humor after topical application. Int J Clin Pract. 2021 Dec;75(12):e14987.
[2]. Effects of sucralfate, lansoprazole, and cimetidine on the delayed healing by hydrocortisone sodium phosphate of chronic gastric ulcers in the rat. Am J Med. 1991 Aug 8;91(2A):15S-19S.

Sodium hydrocortisone phosphate eye drops can rapidly penetrate the human cornea and reach therapeutic concentrations in the aqueous humor within 15 minutes of instillation. [1]
In rats, concurrent use of sucralfate/lansoprazole reversed ulcer healing impairment induced by sodium hydrocortisone phosphate. [2]
Sodium cortisol phosphate is an organic sodium salt, which is the disodium salt of cortisol phosphate. It contains cortisol phosphate (2-).

C21H29O8P-2.2[NA+]

486.40356

486.139

6000-74-4

3863-59-0

441406

White to off-white solid powder

669.9ºC at 760 mmHg

2.775

2

8

3

32

836

7

[Na+].[Na+].O=P(OCC([C@]1(CC[C@H]2[C@@H]3CCC4=CC(CC[C@]4(C)C3[C@H](C[C@]12C)O)=O)O)=O)([O-])[O-]

RYJIRNNXCHOUTQ-OJJGEMKLSA-L

InChI=1S/C21H31O8P.2Na/c1-19-7-5-13(22)9-12(19)3-4-14-15-6-8-21(25,17(24)11-29-30(26,27)28)20(15,2)10-16(23)18(14)19;;/h9,14-16,18,23,25H,3-8,10-11H2,1-2H3,(H2,26,27,28);;/q;2*+1/p-2/t14-,15-,16-,18+,19-,20-,21-;;/m0../s1

disodium;[2-[(8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-10,13-dimethyl-3-oxo-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-17-yl]-2-oxoethyl] phosphate

hydrocortisone sodium phosphate; 6000-74-4; Efcortesol; Cortisol 21-(disodium phosphate); CHEBI:5781; DTXSID5046647; 0388G963HY; DTXCID3026647;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)