TY - JOUR T1 - Effect of probenecid on the distribution, metabolism, and excretion of cidofovir in rabbits. JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 315 LP - 321 VL - 24 IS - 3 AU - K C Cundy AU - Z H Li AU - W A Lee Y1 - 1996/03/01 UR - http://dmd.aspetjournals.org/content/24/3/315.abstract N2 - The effect of concomitant probenecid on the tissue distribution, metabolism, and urinary excretion of cidofovir was examined in New Zealand white rabbits. Two groups of six male rabbits received intravenous [3H]cidofovir (5 mg/kg, 20 mu Ci/kg) alone or with concomitant intravenous probenecid (90 mg/kg). Radioactivity in kidney at 15 min postdose was decreased 70% by probenecid; plasma levels at 15 min postdose were increased 65% by probenecid. These effects were diminished at later time points. The estimated elimination half-life of cidofovir from the kidney was 16 hr in the presence of probenecid and 11 hr without probenecid. Two additional groups of six rabbits received intravenous [14C]cidofovir (15 mg/kg, 100 mu Ci/kg) alone or 1 hr after oral administration of probenecid (90 mg/kg). Radioactivity was highest in the kidney (approximately 700 mu g-eq/g at 30 min postdose). Probenecid did not affect the gross distribution of radioactivity. However, autoradiography of left kidneys revealed localization of the drug in the renal cortex; radioactivity in the cortex at 30 min postdose was decreased 50% by probenecid. These data are consistent with inhibition of tubular secretion of cidofovir by probenecid. More than 73% of the cidofovir dose was recovered in the urine in 24 hr. Urine contained unchanged cidofovir (>97%) and a metabolite coeluting with authentic cidofovir phosphocholine (2%). This metabolite also accounted for approximately 1-4% of the radioactivity in rabbit kidney. ER -