Circadian variation in enoxacin-induced convulsions in mice coadministered with fenbufen.
Susceptibility to enoxacin (80 mg/kg, p.o.)-induced convulsions was examined in mice coadministered with fenbufen (100 mg/kg, p.o.) over 24 hr at 3-hr intervals (light 7:00-19:00 hr). There was a marked circadian variation in the incidence of clonic and tonic convulsions and mortality. The susceptibility to enoxacin was higher around 15:00-18:00 hr and lower around 3:00-9:00 hr; the 50% clonic convulsive dose (CD50) at 9:00 and 15:00 hr was 95.0 and 56.5 mg/kg, respectively, its ratio being 1.64. Under these conditions, brain enoxacin level at 15:00 hr was increased 2.43-fold over that at 9:00 hr 30 min after enoxacin administration. Thus, the change of brain enoxacin may contribute to one of the causes of the above circadian variation.
Masukawa
T
T
Department of Clinical Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, Japan.
Nakanishi
K
K
D000818:Animals; D000890:Anti-Infective Agents / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D001921:Brain / Q000378:metabolism; D002940:Circadian Rhythm / Q000502:physiology*; D004334:Drug Administration Schedule; D004347:Drug Interactions; D015365:Enoxacin / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010654:Phenylbutyrates / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D012640:Seizures / Q000139:chemically induced*
D000890:Anti-Infective Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D010654:Phenylbutyrates; D015365:Enoxacin; C010725:fenbufen