Urinary metabolites of rifabutin, a new antimycobacterial agent, in human volunteers.
1. Metabolites of the antimycobacterial agent 4-deoxo-3,4-[2-spiro-(N-isobutyl-4-piperidyl)]-(1H)-imidazo-(2,5-dihydro )- rifamycin S (rifabutin) were isolated from human urine after administration of a single oral dose of the drug. Some of these metabolites were identified by direct inlet mass spectrometry, 1H-n.m.r. spectrometry and, in two cases, by chromatographic comparison with reference compounds. 2. Unchanged drug, 25-O-deacetyl rifabutin and four other metabolites were identified in human urine. 25-O-Deacetyl rifabutin was the main urinary metabolite, other metabolites were characterized as oxidized, and oxidized-deacetylated derivatives. 3. Routes of metabolic transformation were: (a) deacetylation at position 25, (b) oxidation of methyl groups 31 or 32 or at the piperidine nitrogen, and (c) combination of these.
Cocchiara
G
G
Department of Pharmacokinetics and Metabolism, Farmitalia Carlo Erba Research & Development-Erbamont Group, Milan, Italy.
Strolin Benedetti
M
M
Vicario
G P
GP
Ballabio
M
M
Gioia
B
B
Vioglio
S
S
Vigevani
A
A
D000328:Adult; D000995:Antitubercular Agents / Q000652:urine*; D001711:Biotransformation; D002845:Chromatography; D002855:Chromatography, Thin Layer; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D010084:Oxidation-Reduction; D017828:Rifabutin; D012294:Rifamycins / Q000652:urine*
D000995:Antitubercular Agents; D012294:Rifamycins; D017828:Rifabutin