Metabolism and pharmacokinetics of 14C-pentoxifylline in healthy volunteers

The metabolism and pharmacokinetics of 14C-pentoxifylline (Trental) have been studied in three healthy male volunteers after oral administration of 200 mg (50 microCi). The radiolabelled drug was rapidly absorbed and by 6 h 89.1 +/- 2.4% of the 14C material was excreted in the urine. The dosed 14C material (96.9 +/- 2.2%) was recovered in excreta by 24 h with 93.3 +/- 2.3% in the urine 3.0 +/- 0.2% in the faeces. Peak plasma levels of radioactivity (4.1-6.2 micrograms eq ml-1) occurred 0.25-0.75 h after administration. This radioactivity decayed in a biexponential fashion with an initial half-life of 1.01 +/- 0.13 h and a terminal half-life of 36.06 +/- 16.94 h. The peak plasma levels (0.48-2.25 micrograms ml-1) of parent drug, as measured using a specific gas chromatographic assay also occurred at 0.25-0.75 h and subsequently decayed extremely rapidly with an initial half-life of 0.18 +/- 0.15 h and terminal half-life of 0.76 +/- 0.44 h. Urinary 14C-labelled metabolites were separated by semi-preparative high performance liquid chromatography and characterised by mass spectrometry and by comparison with authentic synthetic compounds. Of the dosed 14C-pentoxifylline, greater than 90% could be identified as characterised metabolites in urine.