Degradation of berenil (diminazene aceturate) in acidic aqueous solution.
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.
Campbell
Michael
M
Centre for Drug Candidate Optimisation, Victorian College of Pharmacy, Monash University (Parkville Campus), 381 Royal Parade, Parkville, Victoria 3052, Australia.
Prankerd
Richard J
RJ
Davie
Ashley S
AS
Charman
William N
WN
D001550:Benzamidines / Q000737:chemistry; D002021:Buffers; D002384:Catalysis; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004133:Diminazene / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry*; D004355:Drug Stability; D041981:Gastrointestinal Tract / Q000737:chemistry; D006207:Half-Life; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D012996:Solutions; D014344:Trypanocidal Agents / Q000008:administration & dosage / Q000737:chemistry*
D001550:Benzamidines; D002021:Buffers; D012996:Solutions; D014344:Trypanocidal Agents; C006500:4-aminobenzamidine; C003915:diminazene aceturate; D004133:Diminazene