ABSORPTION, DISPOSITION AND PRELIMINARY METABOLIC PATHWAY OF C-14 RIFABUTIN IN ANIMALS AND MAN

14C-Rifabutin was given orally to rats, rabbits and monkeys at a dose of 25 mg/kg and to healthy volunteers at a dose of 270 mg. Radioactivity was eliminated by both the renal and faecal routes in all species, with a predominance of the renal route in man and monkeys (50·19% and 46·73% of the dose, respectively, in urine at 96 h), whereas in rats and rabbits a slight predominance of faecal excretion was observed (48·09% and 45·01% of the dose, respectively, at 96 h in faeces; 42·22% and 36·37% in urine). Radioactivity as expired 14CO2 was detected in the rat and accounted for less than 0·5% of the dose within 96 h. The drug was rapidly absorbed and peak plasma radioactivity levels were reached from 1 to 4 h after dosing. Rifabutin was the predominant compound circulating in plasma at the first sampling times, but significant levels of 31-OH rifabutm were detected up to 8-24 h in all species studied. 25-O-deacetyl rifabutin was detected only in rat and man. Polar metabolites were also present, particularly at the later sampling times. The urinary metabolism was studied by radio-HPLC. Rifabutin accounted for 8·5% and 4·6% of the dose in 0-24 h urine of rats and man respectively, whereas in rabbit and monkey urine only traces of this compound were detected. The main known metabolite in all animal species was 31-OH rifabutin; 25-O-deacetyl rifabutin was detected only in rat and man. The remaining urinary radioactivity was mainly due to polar compounds. © 1990, by The British Society for Antimicrobial Chemotherapy.