Metcort Mechanism of Action

Pharmacology: Pharmacodynamics: Methylprednisolone is a synthetic glucocorticoid and a methyl derivative of prednisolone. It is a moderately potent glucocorticoid with only slight mineralocorticoid activity. Methylprednisolone is a potent anti-inflammatory agent with the capacity to profoundly inhibit the immune system. Methylprednisolone 4 mg is equivalent to about 5 mg of prednisolone in terms of anti-inflammatory activity. In addition, methylprednisolone has a lesser tendency to induce sodium and water retention compared with prednisolone.
Pharmacokinetics: The pharmacokinetics of methylprednisolone is linear, independent of the route of administration.
After oral administration, methylprednisolone achieves its maximum plasma concentration in about 1.5-2.3 hrs across doses in healthy adults. Mean oral time to peak concentration is achieved in about 1.1-2.2 hrs. The oral bioavailability of methylprednisolone is 82-89%.
Methylprednisolone is widely distributed throughout the body and is described by a 2-compartment model. The mean volume of distribution of methylprednisolone ranges from 41-61.5 L in adult volunteers.
Similar to many CYP3A4 substrates, methylprednisolone may also be a substrate for the adenosine triphosphate (ATP)-binding cassette (ABC) transport protein p-glycoprotein which may influence tissue distribution and interactions with other medicines.
Methylprednisolone is widely distributed into tissues and is bound to plasma protein (approximately 77%). It crosses the blood-brain barrier into the central nervous system with peak CSF levels being 5-6% of the corresponding plasma levels. It also crosses the placenta and is secreted in breast milk.
Methylprednisolone is extensively metabolized in the liver to inactive metabolites, mainly 20α-hydroxymethylprednisolone and 20β-hydroxymethylprednisolone. Metabolism in the liver occurs primarily via the CYP3A4 enzyme.
The mean elimination half-life (t_½) for total methylprednisolone is in the range of 1.8-5.2 hrs.
Radiolabeled 6-methylprednisolone was administered IV to 6 cancer patients. Seventy-five percent (75%) of total radioactivity was recovered in the urine after 96 hrs and 9% in the feces after 5 days. Twenty percent (20%) of the total dose was excreted in the bile; however, the time course was not cited.