Absorption, disposition and preliminary metabolic pathway of 14C-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 rifabutin 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.
Battaglia
R
R
Farmitalia Carlo Erba, R&D-Erbamont Group, Milan, Italy.
Pianezzola
E
E
Salgarollo
G
G
Zini
G
G
Strolin Benedetti
M
M
D000328:Adult; D000818:Animals; D000995:Antitubercular Agents / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D005243:Feces / Q000737:chemistry; D005260:Female; D006801:Humans; D006868:Hydrolysis; D007408:Intestinal Absorption; D008252:Macaca fascicularis; D008297:Male; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D017828:Rifabutin; D012294:Rifamycins / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine; D013045:Species Specificity
D000995:Antitubercular Agents; D012294:Rifamycins; D017828:Rifabutin