Oral formulations of adefovir dipivoxil: in vitro dissolution and in vivo bioavailability in dogs

Journal of Pharmaceutical Sciences
Kenneth C CundyJ P Shaw

Abstract

The effect of formulation on oral bioavailability of the antiviral nucleotide analogue adefovir from the prodrug adefovir dipivoxil was examined in beagle dogs. A suspension formulation of adefovir dipivoxil granules was administered to five fasted male beagle dogs (250 mg prodrug per dog; 135.7 mg-equiv of adefovir per dog). Tablets prepared from the same granulation (batch B94) were administered at 2 x 125 mg prodrug per dog. In addition, the same tablets were administered to dogs in the fed state or following pentagastrin pretreatment. Two further tablet batches (H94 and D501) with slight formulation changes were also evaluated in pentagastrin pretreated dogs (n = 5). Concentrations of adefovir in plasma were determined by HPLC following fluorescence derivatization. Tablet dissolution was examined at pH 2.0. One batch of adefovir dipivoxil tablets showed a 5-fold slower dissolution rate in vitro (B94 = H94 > D501). Adefovir dipivoxil was completely converted to adefovir following oral absorption in dogs. The oral bioavailability of adefovir from the suspension was 35.0 +/- 8.9%. The oral bioavailability of adefovir from the tablet formulation was 34.7 +/- 10.3%, 37.2 +/- 4.5%, and 44.9 +/- 5.9% in fasted dogs, fed dogs and f...Continue Reading

References

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Citations

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