Dexamethasone EP Impurity E

Absorption

Following oral administration with food, the median Tmax of vamorolone is approximately 2 hours.
The co-administration of vamorolone with a high-fat, high-calorie meal reduced Cmax by 18%, increased AUC by 13%, and delayed Tmax by one hour. The co-administration of vamorolone with a low-fat, low-calorie meal reduced Cmax by 4%, increased AUC by 14%, and delayed Tmax by one hour.

Toxicity

Specific data regarding vamorolone overdosage are not readily available. Prescribing information recommends supportive and symptomatic treatment in the event of suspected vamorolone overdose, with consideration given to gastric lavage or emesis if clinically appropriate.

The Uses of Dexamethasone EP Impurity E

A related intermediate of Prednisolone (P703740).

Background

Vamorolone is a novel and fully synthetic glucocorticoid developed by Santhera Pharmaceuticals. It is used to manage inflammation and immune dysregulation in patients with Duchenne muscular dystrophy (DMD), a neuromuscular disorder characterized by the insidious regression of neuromuscular function and the most common form of muscular dystrophy in the United States. Corticosteroid therapy is the current standard of care for DMD despite relatively high rates of adverse effects. Vamorolone is positioned as having a more tolerable adverse effect profile than other corticosteroids owing to its unique receptor binding profile, thus providing an additional treatment option in patients for whom corticosteroid adverse effects are intolerable or otherwise unacceptable.
Vamorolone was approved by the FDA in October 2023 for the management of DMD in patients ≥2 years of age.

Indications

Vamorolone is indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients ≥2 years of age.

Pharmacokinetics

In clinical studies, treatment with vamorolone induced a dose-dependent decrease in morning cortisol levels and a dose-dependent increase in leukocyte and lymphocyte counts.

Metabolism

Vamorolone is subject to multiple metabolic pathways, including glucuronidation, hydroxylation, and reduction. Its metabolism is mediated through CYP3A4, CYP3A5, CYP2C8, UGT1A3, UGT2B7, and UGT2B17. Glucuronides - formed via direct glucuronidation and hydrogenation with subsequent glucuronidation - are the main metabolites in the plasma and urine.