Absorption, disposition, and urinary metabolism of 14C-rifabutin in rats

Abstract

14C-rifabutin was given orally (25 mg/kg) and intravenously (i.v.) (10 mg/kg) to female Sprague-Dawley rats. Radioactivity was eliminated by both the renal and fecal routes, amounting to 44.49 and 43.39% of the dose, respectively, in urine and feces at 96 h after the oral dose and to 47.81 and 40.76% of the dose, respectively, in urine and feces after the i.v. dose. Differences between the two routes of administration were negligible. Tissue distribution of radioactivity after the oral dose was investigated by the combustion technique. At 2 h, the highest concentration of radioactivity was observed in the liver, followed by the lung, abdominal adipose tissue, and spleen, whereas at 72 h, the sequence was abdominal adipose tissue, liver, spleen, bone marrow, and lung. Brain levels of radioactivity were very low. The results of whole-body autoradiography after i.v. administration confirmed the above. Whole-body autoradiography of pregnant rats showed higher concentrations of radioactivity in the uterus than in the placenta and trace levels in the fetuses up to 8 h. Radioactivity was absent in the amniotic fluid. The urinary metabolism was studied by radio-high-pressure liquid chromatography. Rifabutin accounted for 7.4 and 7.2% of the dose in 0- to 48-h urine after oral and i.v. administration, respectively. Metabolites 31-OH rifabutin and 25-O-deacetyl rifabutin amounted to 4.3 and 1.6% of the dose, respectively, after oral administration and to 2.6 and 0.7% of the dose, respectively, after i.v. administration. The remaining urinary radioactivity was mainly due to polar compounds.