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.
Centre for Drug Candidate Optimisation, Victorian College of Pharmacy, Monash University (Parkville Campus), 381 Royal Parade, Parkville, Victoria 3052, Australia.
Michael
M
Campbell
Richard J
RJ
Prankerd
Ashley S
AS
Davie
William N
WN
Charman
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