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Adefovir dipivoxil is a prodrug of adefovir. Adefovir is an acyclic nucleotide analog of adenosine monophosphate which is phosphorylated to the active metabolite adefovir diphosphate by cellular kinases. Adefovir diphosphate inhibits HBV DNA polymerase (reverse transcriptase) by competing with the natural substrate deoxyadenosine triphosphate and by causing DNA chain termination after its incorporation into viral DNA. The inhibition constant (Ki) for adefovir diphosphate for HBV DNA polymerase was 0.1 _M. Adefovir diphosphate is a weak inhibitor of human DNA polymerases _ and _ with Ki values of 1.18 _M and 0.97_M, respectively.
Adefovir dipivoxil a diester prodrug of adefovir. Adefovir is an acyclic nucleotide analog with activity against human hepatitis B virus (HBV). The concentration of adefovir that inhibited 50% of viral DNA synthesis (IC50) in vitro ranged from 0.2 to 2.5 _M in HBV transfected human hepatoma cell lines. The combination of adefovir with lamivudine showed additive anti-HBV activity.
Following oral administration, adefovir dipivoxil is rapidly converted to adefovir. Forty-five percent of the dose is recovered as adefovir in the urine over 24 hours at steady state following 10 mg oral doses. Adefovir is not a substrate of the cytochrome P450 enzymes.
Renal tubular nephropathy characterized by histological alterations and/or increases in BUN and serum creatinine was the primary dose-limiting toxicity associated with administration of adefovir dipivoxil in animals. Nephrotoxicity was observed in animals at systemic exposures approximately 3Ð10 times higher than those in humans at the recommended therapeutic dose of 10 mg/day.
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LGM currently offers Monoclonal Antibodies (mAbs) for non-GMP/R&D use. Please inquire about Monoclonal Antibodies produced under GMP conditions.
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