Hydrocortisone:Application,Bioactivities,Pharmacokinetics

Hydrocortisone, also known as Cortisol, is an important adrenal glucocorticoid. Its pharmacological action is to form a steroid-receptor complex by diffusing on target cells and combining with its receptor. The activated steroid-receptor complex acts as an activator of gene transcription, and combines with specific sequence chain on DNA in the form of dimer to regulate gene transcription, increase the production of mRNA and use it as a template to synthesize corresponding proteins, which realize the physiological and pharmacological effects of steroid hormones in target cells. Hydrocortisone can affect glucose metabolism and has anti-inflammatory, antiviral, anti-shock and anti-allergic effects. Its appearance is as follows:

Figure 1 Appearance of Hydrocortisone.

The ₃ and three times with water, dried over MgSO₄, filtered, and concentrated. Column chromatography afforded the pure Hydrocortisone with the wash, and the yield is 54%.

Application

Hydrocortisone is a major glucocorticoid hormone in mammals, which is essential for life. Hydrocortisone has multiple uses, and it is an steroid drug in the cilinical application.Hydrocortisone has a distinct circadian rhythm which is regulated by the main circadian oscillator in the suprachiasmatic nucleus (SCN) located in the hypothalamus. Normal individuals have very low or undetectable levels of circulating Hydrocortisone at midnight; levels then increase overnight to peak first thing in the morning. Hydrocortisone levels then decline slowly throughout the day [2]. It is mainly used for the replacement treatment of adrenocortical hypofunction and the treatment of congenital adrenocortical hyperplasia. It can also be used for rheumatoid arthritis, rheumatic fever, gout, bronchial asthma, allergic diseases, and for severe infection and anti-shock treatment. Hydrocortisone is also the raw material for the preparation of several other important steroid drugs.

Bioactivities

Hydrocortisone can reduce and prevent the inflammatory reaction of the body by reducing the permeability of the body's capillaries, stabilizing the activity of lysosome membrane, and preventing the accumulation of white blood cells in the inflammatory site, so as to alleviate the inflammation [3]. Moreover, it can prevent or inhibit the cell-mediated immune response by accelerating the apoptosis of lymphocytes in the body and preventing the formation of mononuclear macrophages [4].

Pharmacokinetics

The pharmacokinetics of 20 mg hydrocortisone were studied after IV and oral administration [5]. Endogenous hydrocortisone was suppressed by dexamethasone administration. Hydrocortisone concentrations were measured in plasma and saliva. After IV administration, hydrocortisone was eliminated with a total body clearance of 18 L/hr and a half-life of 1.7 hr. The volume of distribution was 34 L. Oral bioavailability averaged 96%. Absorption was rapid, achieving maximum hydrocortisone levels of 300 ng/mL after 1 hour. Saliva levels were not proportional to plasma levels, but could be shown to reflect free, non-protein bound hydrocortisone concentrations in plasma.

[2]Krieger et al. Characterization of the normal temporal pattern of plasma corticosteroid levels. The Journal of Clinical Endocrinology and Metabolism 1971; 32: 266–284.

[3]Debono et al. Modified-release hydrocortisone to provide circadian cortisol profiles. J Clin Endocrinol Metab 2009;94:1548-1554.

[4]Newell-Price et al.Modified-release hydrocortisone for circadian therapy: a proof-of-principle study in dexamethasone-suppressed normal volunteers. Clinical Endocrinology 2008; 68: 130–135.

[5]Hartmut et al. Pharmacokinetics and oral bioavailability of hydrocortisone. The Journal of Clinical Pharmacology 1991, 31(5): 395-489.

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