Clobetasol propionate has an IC50 of 15.6 μM against CYP3A4[1]. Clobetasol propionate (1 μM; 24 hours) did not raise the levels of CYP3A4 protein, but it preferentially inhibits CYP3A5. No cell lines (AsPC-1 wild type (WT), CYP3A5 overexpressing AsPC-1CYP3A5–/– cells ("3A5–/– + 3A5OE” cells), and AsPC-1CYP3A5–/– CYP3A4–overexpressing cells ("3A5–/– + 3A4OE” cells) were affected by clobetasol propionate [1].

In a transplant SCID mouse model of human psoriatic skin, clobetasol propionate (topically administered; applied daily for 14 days) decreased epidermal thickness in both normal and psoriatic skin [3].

Absorption, Distribution and Excretion
Twice daily application of clobetasol foam leads to a Cmax of 59±36pg/mL with a Tmax of 5 hours. Clobetasol cream showed an increase in clobetasol concentrations from 50.7±96.0pg/mL to 56.3±104.7pg/mL.
Corticosteroids are eliminated predominantly in the urine.
Data regarding the volume of distribution of clobetasole propionate are not readily available.
Data regarding the clearance of clobetasol propionate are not readily available.

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Metabolism / Metabolites
The metabolism of clobetasol propionate is not well studied but it does induce metabolic enzymes, even when delivered topically. The metabolism of clobetasol propionate is predicted to follow similar metabolic pathways to other corticosteroids including the addition of oxygen, hydrogen, glucuronides, and sulfates to form water soluble metabolites.

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Biological Half-Life
Data regarding the half life of clobetasol propionate are not readily available.

Protein Binding
Data regarding the protein binding of clobetasol propionate are not readily available. Corticosteroids are generally bound to corticosteroid binding globulin and serum albumin in plasma.

[1]. Clobetasol Propionate Is a Heme-Mediated Selective Inhibitor of Human Cytochrome P450 3A5. J Med Chem. 2020 Feb 13;63(3):1415-1433.

[2]. Topical clobetasol propionate in the treatment of psoriasis: a review of newer formulations. Am J Clin Dermatol. 2009;10(6):397-406.

[3]. Anti-CD11a ameliorates disease in the human psoriatic skin-SCID mouse transplant model: comparison of antibody to CD11a with Cyclosporin A and clobetasol propionate. Lab Invest. 2001 Sep;81(9):1253-61.

Clobetasol Propionate can cause developmental toxicity and female reproductive toxicity according to state or federal government labeling requirements.
Clobetasol propionate is the 17-O-propionate ester of clobetasol. A potent corticosteroid, it is used to treat various skin disorders, including exzema and psoriasis. It has a role as an anti-inflammatory drug. It is an 11beta-hydroxy steroid, a 20-oxo steroid, a glucocorticoid, a fluorinated steroid, a 3-oxo-Delta(1),Delta(4)-steroid and a chlorinated steroid. It is functionally related to a clobetasol and a propionic acid.
Clobetasol propionate is a prednisolone derivative with higher specificity for glucocorticoid receptors than mineralocorticoid receptors. It has demonstrated superior activity compared to [fluocinonide] and was first described in the literature in 1974. Clobetasol Propionate was granted FDA approval on 27 December 1985.
Clobetasol Propionate is the propionate salt form of clobetasol, a topical synthetic corticosteroid with anti-inflammatory, anti-pruritic, and vasoconstrictive properties. Clobetasol propionate exerts its effect by binding to cytoplasmic glucocorticoid receptors and subsequently activates glucocorticoid receptor mediated gene expression. This results in synthesis of certain anti-inflammatory proteins, while inhibiting the synthesis of certain inflammatory mediators. Specifically, clobetasol propionate appears to induce phospholipase A2 inhibitory proteins, thereby controlling the release of the inflammatory precursor arachidonic acid from membrane phospholipids by phospholipase A2.
A derivative of PREDNISOLONE with high glucocorticoid activity and low mineralocorticoid activity. Absorbed through the skin faster than FLUOCINONIDE, it is used topically in treatment of PSORIASIS but may cause marked adrenocortical suppression.
See also: Clobetasol (has active moiety); Clobetasol propionate; niacinamide (component of); Clobetasol propionate; coal tar; salicylic acid (component of) ... View More ...

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Drug Indication
Clobetasol propionate is indicated to treat moderate to severe plaque psoriasis as well as inflammatory and pruritic manifestations of corticosteroid responsive dermatoses.
FDA Label

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Mechanism of Action
The short term effects of corticosteroids are decreased vasodilation and permeability of capillaries, as well as decreased leukocyte migration to sites of inflammation. Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days. Glucocorticoids inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A2, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-10. Lower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive. High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels.

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Pharmacodynamics
Corticosteroids bind to the glucocorticoid receptor, inhibiting pro-inflammatory signals, and promoting anti-inflammatory signals. Clobetasol propionate is generally applied twice daily so the duration of action is long. Corticosteroids have a wide therapeutic window as patients may require doses that are multiples of what the body naturally produces. Patients taking corticosteroids should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.

C25H32CLFO5

466.97

466.192

25122-46-7

25122-46-7 (propionate);25122-41-2;

32798

White to off-white solid powder

1.3±0.1 g/cm3

569.0±50.0 °C at 760 mmHg

195.5-197ºC

297.9±30.1 °C

0.0±3.5 mmHg at 25°C

1.560

3.98

1

6

5

32

929

8

CCC(=O)O[C@@]1([C@H](C[C@@H]2[C@@]1(C[C@@H]([C@]3([C@H]2CCC4=CC(=O)C=C[C@@]43C)F)O)C)C)C(=O)CCl

FKWXHUWJFNMNSE-NQNWYGNOSA-N

InChI=1S/C25H32ClFO5/c1-5-21(31)32-23(4)14(2)10-18-17-7-6-15-11-16(28)8-9-22(15,3)25(17,27)19(29)12-24(18,23)20(30)13-26/h8-9,11,14,17-19,29H,5-7,10,12-13H2,1-4H3/t14-,17-,18-,19-,22-,23+,24-,25-/m0/s1

(8S,9R,10S,11S,13R,14S,16S,17R)-13-(2-chloroacetyl)-9-fluoro-11-hydroxy-10,16,17-trimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl propionate

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)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.35 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (5.35 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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