title: Dosing-time-dependent variation in biliary excretion of flomoxef in rats.
abstract: We previously reported that the biliary excretion of flomoxef, an oxacephem antibiotic, was greater after dosing at 21:00 than at 09:00 h in diurnally active human subjects. The present study was undertaken to examine whether the biliary excretion of flomoxef is also dependent on its dosing time in rats. Adult male Wistar rats were housed under light on at 07:00 h and off at 19:00 h. Bile fluid was completely drained through a polyethylene catheter from conscious animals. Flomoxef (20 mg/kg) was injected into the tail vein at 09:00 or 21:00 h by a cross-over design, and drained bile fluid was collected for 8 h after each dosing. The maximum concentration of biliary flomoxef was significantly greater and its total excretion tended to be greater after dosing at 09:00 than 21:00 h. These results suggest the biliary excretion of flomoxef is enhanced after dosing at the beginning of the rest period in rats, as it is in humans.
authors.affiliation: Department of Clinical Pharmacology, Jichi Medical School, Tochigi, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Hishikawa
authors.forename: Koh-ichi
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Eiji
authors.initials: E
authors.lastname: Kobayashi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kumagai
authors.forename: Akio
authors.initials: A
authors.lastname: Fujimura
mesh_terms: D000818:Animals; D001646:Bile / Q000737:chemistry; D002511:Cephalosporins / Q000378:metabolism*; D002940:Circadian Rhythm / Q000502:physiology*; D005704:Gallbladder / Q000378:metabolism*; D006801:Humans; D008297:Male; D017440:Photoperiod; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D002511:Cephalosporins; C045693:flomoxef