A human capecitabine excretion balance and pharmacokinetic study after administration of a single oral dose of C-14-labelled drug

An excretion balance and pharmacokinetic study was conducted in cancer pati ents with solid tumors who received a single oral dose of capecitabine of 2 000 mg including 50 mu Ci of C-14-radiolabelled capecitabine. Blood, urine and fecal samples were collected until radioactive counts had fallen to bel ow 50 dpm/mL in urine, and levels of intact drug and its metabolites were m easured in plasma and urine by LC/MS-MS (mass spectrometry) and F-19-NMR (n uclear magnetic resonance) respectively. Based on the results of the 6 elig ible patients enrolled, the dose was almost completely recovered in the uri ne (mean 95.5%, range 86-104% based on radioactivity measurements) over a p eriod of 7 days after drug administration. Of this, 84% (range 71-95) was r ecovered in the first 12 hours. Over this time period, 2.64% (0.69-7.0) was collected in the feces. Over a collection period of 24-48 h, a total of 84 .2% (range 80-95) was recovered in the urine as the sum of the parent drug and measured metabolites (5'-DFCR, 5'-DFUR, 5-FU, FUH2, FUPA, FBAL). Based on the radioactivity measurements of drug-related material, absorption is r apid (t(max) 0.25-1.5 hours) followed by a rapid biphasic decline. The pare nt drug is rapidly converted to 5-FU, which is present in low levels due to the rapid metabolism to FBAL, which has the longest half-life. There is a good correlation between the levels of radioactivity in the plasma and the levels of intact drug and the metabolites, suggesting that these represent the most abundant metabolites of capecitabine. The absorption of capecitabi ne is rapid and almost complete. The excretion of the intact drug and its m etabolites is rapid and almost exclusively in the urine.