Activation of beclomethasone dipropionate by hydrolysis to beclomethasone-17-monopropionate

Biopharm Drug Dispos. 1990 Jul;11(5):381-94. doi: 10.1002/bdd.2510110503.

Abstract

The relative affinity of beclomethasone (B), beclomethasone-17-monopropionate (17-BMP), beclomethasone-21-monopropionate (21-BMP), and beclomethasone dipropionate (BDP) has been determined. BDP binds to the glucocorticoid receptor with about half the affinity of the potent glucocorticoid dexamethasone (Dexa), B was found to be 0.75 times less active than Dexa. The 21-BMP has no binding affinity whereas the 17-BMP is about 13 times as potent as Dexa. The affinity data indicate that metabolism of BDP to 17-BMP is an important activation step. To evaluate the relationship between local and systemic activity incubation studies with BDP in human lung, simulated gastric and intestinal fluid and plasma were performed. In cytosol from human lung cells BDP is hydrolysed rapidly to the more stable 17-BMP. During gastric passage BDP is stable but is immediately hydrolysed to 17-BMP in intestinal fluid. In human plasma BDP is hydrolysed to 17-BMP and an interesterification of 17-BMP to the inactive 21-BMP was also found.

MeSH terms

  • Beclomethasone / analogs & derivatives*
  • Beclomethasone / metabolism*
  • Biotransformation
  • Chromatography, High Pressure Liquid
  • Cytosol / metabolism
  • Gastric Mucosa / metabolism
  • Half-Life
  • Humans
  • Hydrolysis
  • Intestinal Mucosa / metabolism
  • Lung / metabolism
  • Receptors, Glucocorticoid / metabolism

Substances

  • Receptors, Glucocorticoid
  • beclomethasone 17-monopropionate
  • Beclomethasone