title: Effect of a new rifamycin derivative, rifalazil, on liver microsomal enzyme induction in rat and dog.
abstract: 1. The effect of a new rifamycin derivative, rifalazil (KRM-1648), on liver microsomal enzyme induction was studied in rat and dog with repeated oral administration of the compound. Relative liver weight, cytochrome b5 and P450 contents, enzyme activities of NADPH-cytochrome c reductase, aniline hydroxylase, p-nitroanisole O-demethylase, aminopyrine N-demethylase, and erythromycin N-demethylase were measured. 2. In rat, rifalazil treatment at 300 mg/kg/day for 10 days increased cytochrome b5 content but it did not affect liver weight, P450 content or enzyme activities. In contrast, rifampicin and rifabutin increased relative liver weights, cytochrome contents and enzyme activities under similar conditions. 3. In dog, rifalazil did not affect any parameters at 30 or 300 mg/kg/day for 13 weeks. 4. These findings indicate that rifalazil is not an enzyme inducer in rat and dog. This property differs from other rifamycin derivatives such as rifampicin and rifabutin.
authors.affiliation: Takasago Research Laboratories, Research Institute, Kaneka Corp., Hyogo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Mae
authors.forename: K
authors.initials: K
authors.lastname: Hosoe
authors.forename: T
authors.initials: T
authors.lastname: Yamamoto
authors.forename: T
authors.initials: T
authors.lastname: Hidaka
authors.forename: T
authors.initials: T
authors.lastname: Ohashi
authors.forename: J M
authors.initials: JM
authors.lastname: Kleeman
authors.forename: P E
authors.initials: PE
authors.lastname: Adams
mesh_terms: D000818:Animals; D000904:Antibiotics, Antitubercular / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism; D015786:Cytochromes b5 / Q000096:biosynthesis / Q000378:metabolism; D004285:Dogs; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000096:biosynthesis* / Q000378:metabolism; D009251:NADPH-Ferrihemoprotein Reductase / Q000096:biosynthesis / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017828:Rifabutin / Q000494:pharmacology; D012293:Rifampin / Q000494:pharmacology; D012294:Rifamycins / Q000494:pharmacology*
chemical_list: D000904:Antibiotics, Antitubercular; D012294:Rifamycins; C068980:KRM 1648; D017828:Rifabutin; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D009251:NADPH-Ferrihemoprotein Reductase; D012293:Rifampin