Degradation of berenil (diminazene aceturate) in acidic aqueous solution

J Pharm Pharmacol. 2004 Oct;56(10):1327-32. doi: 10.1211/0022357044409.

Abstract

The trypanocide berenil was assessed for chemical stability over the pH range 1-8 at 37 degrees C and 0.2 M ionic strength. It was found to be sufficiently unstable under acid conditions that its therapeutic efficacy is most likely severely compromised when administered orally. At pH 3, the half-life was 35 min, decreasing to 1.5 min at pH 1.75. Reaction rate constants were corrected for the effects of buffer catalysis and were found to range from 2.00 min(-1) at pH 1 to 6.1 x 10(-6) min(-1) at pH 8. The pH-rate profile displayed a region (pH 1-4) where specific acid catalysis was dominant, followed by a transitional region (pH 5-7), and finally a region (pH >7) where uncatalysed degradation was most important. It is recommended that berenil be enteric coated for formulations to be used in treating Third World parasitic diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzamidines / chemistry
  • Buffers
  • Catalysis
  • Chemistry, Pharmaceutical
  • Chromatography, High Pressure Liquid
  • Diminazene / administration & dosage
  • Diminazene / analogs & derivatives*
  • Diminazene / chemistry*
  • Drug Stability
  • Gastrointestinal Tract / chemistry
  • Half-Life
  • Hydrogen-Ion Concentration
  • Hydrolysis
  • Solutions
  • Trypanocidal Agents / administration & dosage
  • Trypanocidal Agents / chemistry*

Substances

  • Benzamidines
  • Buffers
  • Solutions
  • Trypanocidal Agents
  • 4-aminobenzamidine
  • diminazene aceturate
  • Diminazene