Norpredninol

Norpredninol is a synthetic glucocorticoid steroid that was first reported in the early 1970s during the development of more selective anti‑inflammatory drugs. The compound is structurally related to prednisolone but lacks the 3‑keto group, giving it a distinctive pattern of hydrogen bonding that enhances its affinity for the glucocorticoid receptor. Its chemical formula is C21H28O4 and it is typically sold as its sodium salt for pharmaceutical preparations.

In vitro studies show that norpredninol activates the glucocorticoid receptor with a potency only slightly lower than prednisolone, yet it exhibits a reduced mineralocorticoid activity. This differential binding profile translates into a lower risk of fluid retention and hypertension when compared with many older steroids. Pharmacokinetic analyses indicate that the drug is absorbed rapidly when administered orally or intravenously, with peak plasma concentrations reached within 30 minutes. Norpredninol is metabolized primarily in the liver by the CYP3A4 enzyme family, and its metabolites are excreted largely via bile and urine.

Clinically, norpredninol has been used primarily for ocular inflammation, such as iritis and uveitis, because its potency allows for lower dosing while maintaining therapeutic efficacy. It has also been prescribed for moderate to severe rheumatoid arthritis and other inflammatory arthropathies in some countries, though its use has declined in favor of newer synthetic steroids with improved safety profiles. Side‑effect data indicate that, similar to other glucocorticoids, chronic therapy can lead to osteoporosis, adrenal suppression, and skin thinning, although the incidence is reported to be lower than with long‑term prednisolone treatment.

Research into norpredninol has focused on developing topical formulations that maximize ocular penetration while minimizing systemic absorption. In addition, several analogs have been synthesized to further reduce mineralocorticoid activity, aiming to create a steroid with minimal cardiovascular adverse effects. The compound remains a subject of interest in pharmacological studies aimed at refining the therapeutic window for anti‑inflammatory steroid therapy.