Pharmacologic analysis of the ip administration of fludarabine phosphate in the swine

Fludarabine phosphate, an investigational water-soluble adenosine analog, was administered ip to five miniature swine at doses of 10, 16, and 25 mg/m2. Blood and peritoneal fluid samples were collected for 4 hours following drug administration and were submitted to high-performance liquid chromatographic analysis for the concentrations of the dephosphorylated derivative, 2-fluoro-ara-A. Peak peritoneal fluid concentrations of 2-fluoro-ara-A ranged from 7.72 to 18.01 micrograms/ml at the doses tested; peritoneal fluid areas-under-the-curve (AUCs) ranged from 19.23 to 47.33 micrograms X hour/ml. The peak serum concentrations of 2-fluoro-ara-A ranged from 0.15 to 0.46 micrograms/ml; serum AUCs ranged from 0.51 to 1.2 micrograms X hour/ml. The ip administration of fludarabine phosphate results in a 28-62-fold peak peritoneal concentration advantage over peak serum concentrations and a 20-53-fold advantage for peritoneal over serum AUCs. Comparison of data generated in this swine study to data from pilot studies of the ip administration of fludarabine phosphate in humans will be of interest.