Kinetic studies of the degradation of oxycarbonyloxymethyl prodrug of adefovir and tenofovir in solution

Abstract

The decomposition kinetics of bis-POC PMEA and bis-POC PMPA followed pseudo-first order kinetics with the corresponding mono-POC ester detected as the only observable degradation product for all the pH values studied. The rates of hydrolysis of bis-POC PMEA over the pH range studied was described by ko = kHfAH[H+] + kH2OfAH + k′H2OfA + kOHfA [OH-]. The 18O incorporation studies revealed that hydrolysis of bis-POC PMEA at pH 7.0 primarily proceeds via P-O cleavage with an additional minor pathway involving C-O bond cleavage. Hydrolysis of bis-POC PMPA was found to be about 2 fold slower than bis-POC PMEA at pH values above 6.0.