Identification and antimicrobial activity of urinary metabolites of a rifamycin derivative in dog.
1. Three metabolites of the antimicrobial agent 3'-hydroxy-5'-(4-isobutyl-1-piperazinyl)benzoxazinorifamycin (KRM-1648) were isolated from dog urine obtained after administration of a single oral dose. These metabolites of KRM-1648 were identified by mass spectrometry and 1H and 13C-nmr spectrometry. 2. Three metabolites of KRM-1648 were identified as 25-deacetyl KRM-1648, 30-hydroxy KRM-1648 and 25-deacetyl-30-hydroxy KRM-1648. 3. The antimicrobial activities of 25-deacetyl KRM-1648 were comparable with those of the parent compound, whereas 30-hydroxy KRM-1648 was equipotent and 2-8-fold less active than the parent compound against bacteria and mycobacteria, respectively.
Hosoe
K
K
Takasago Research Laboratories, Hyogo, Japan.
Mae
T
T
Yamashita
K
K
Fujii
K
K
Yamane
T
T
Hidaka
T
T
Ohashi
T
T
D000284:Administration, Oral; D000818:Animals; D000904:Antibiotics, Antitubercular / Q000494:pharmacology* / Q000652:urine*; D002247:Carbon Isotopes; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008826:Microbial Sensitivity Tests; D009161:Mycobacterium / Q000187:drug effects; D012294:Rifamycins / Q000494:pharmacology* / Q000652:urine*
D000904:Antibiotics, Antitubercular; D002247:Carbon Isotopes; D012294:Rifamycins; C068980:KRM 1648