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 rates of hydrolysis of bis-POC PMEA over the pH range studied was described by [formula: see text] 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.
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Gilead Sciences Inc., 335 Lakeside Drive, Foster City, California 94404, USA.
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D000225:Adenine / Q000031:analogs & derivatives* / Q000737:chemistry*; D000998:Antiviral Agents / Q000737:chemistry*; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000737:chemistry*; D011355:Prodrugs / Q000737:chemistry*; D012996:Solutions; D000068698:Tenofovir
D000998:Antiviral Agents; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D011355:Prodrugs; D012996:Solutions; C111774:bis(isopropyloxymethylcarbonyl) 9-(2-phosphonomethoxypropyl)adenine; C442773:bis(isopropyloxymethylcarbonyl)-9-(2-phosphonomethoxyethyl)adenine; C053001:adefovir; D000068698:Tenofovir; D000225:Adenine