Lack of potentiation with felbinac patch on the convulsive toxicity of enoxacin in rats.
We investigated the possible potentiation of the convulsive toxicity of enoxacin (ENX) by the concomitant topical application of a felbinac (FLB) patch in rats. A felbinac patch (Seltouch; 0.5%, 3 cm x 4 cm) was attached on the back of rats where their hair has been removed. ENX was infused from the left jugular vein at 8 h after the application of FLB patch under an unanesthetized and unstrained condition. Blood, CSF and brain samples were collected at the occurrence of convulsion, and ENX concentrations of each part were determined. As a result, no significant potentiation by FLB patch was found in the onset time of convulsion or in the ENX concentration of each part. Moreover, based on the assumption that there are no inter-species differences in ENX concentration in the brain at the occurrence of a convulsion (Cbr), the predicted plasma ENX concentration required to elicit convulsions in humans, which was estimated from the Cbr and Kp value of ENX in the brain of rats, was 20 times higher than the therapeutic plasma level.
Ohtani
H
H
Department of Pharmacy, University of Tokyo Hospital, Faculty of Medicine, Japan.
Noma
S
S
Kawakami
J
J
Sawada
Y
Y
Iga
T
T
D000279:Administration, Cutaneous; D000818:Animals; D000890:Anti-Infective Agents / Q000493:pharmacokinetics / Q000633:toxicity*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D001921:Brain / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003292:Convulsants / Q000633:toxicity*; D004357:Drug Synergism; D015365:Enoxacin / Q000493:pharmacokinetics / Q000633:toxicity*; D008297:Male; D010648:Phenylacetates / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
D000890:Anti-Infective Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003292:Convulsants; D010648:Phenylacetates; D015365:Enoxacin; C012776:biphenylylacetic acid