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

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 rat es of hydrolysis of bis-POC PMEA over the pH range studied was described by k(o) = k(H)f(AH)[H+] + k(H20)f(AH) + k'(H2O)f(A) + k(OH)f(A) [OH-]. The O-18 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 ab out 2 fold slower than bis-POC PMEA at pH values above 6.0.