[Experimental study on the hepatobiliary kinetics and excretion of temafloxacin. Evidence for production of active metabolites by the rabbit liver].
Temafloxacin is a new fluoroquinolone derivative currently under evaluation. Its hepatobiliary disposition remains undefined as yet. The present study represents an experimental approach to this issue. Six isolated rabbit liver preparations were perfused for three hours with reconstituted and oxygenated blood in a closed circuit. A the onset of the procedures, temafloxacin 10 mg were added to the circulating blood. Both bile and blood were sampled throughout the perfusion time, and liver fragments were taken at the end of the experiments. Temafloxacin levels were measured by HPLC in serum and hepatic tissue, and by both HPLC and microbiological assay in bile. The percentage of drug undergoing hepatic biotransformation appeared to be high, i.e. 58.3%. This finding is substantiated by the comparison of temafloxacin levels in bile, as provided by HPLC and microbiological assay, the latter yielding concentrations twice as high (biliary peak: 33.5 +/- 2.8 micrograms/ml versus 19.3 +/- 3.1 micrograms/ml by HPLC assay) as those obtained by HPLC (p less than 0.05). Consistently, the average amount of temafloxacin excreted into the bile (0-3 h) was, respectively, 92 micrograms (0.9% of the dose) and 204 micrograms (2.0%) as determined by HPLC and microbiological methods (p less than 0.05); this statistically significant difference suggests the presence of active metabolites in bile. The presented results bring out evidence for substantial biotransformation of temafloxacin by Rabbit liver. Extrapolation to other species, however, would be hazardous; further pharmacokinetic studies are needed in order to assess the relevance of these findings in humans.
Brogard
J M
JM
Laboratoire de Pathologie Interne et Expérimentale de la Clinique Médicale B, Strasbourg.
Westphal
J F
JF
Koechlin
C
C
Jehl
F
F
Dorner
M
M
Blickle
J F
JF
Monteil
H
H
D042462:4-Quinolones; D000818:Animals; D000890:Anti-Infective Agents / Q000097:blood / Q000493:pharmacokinetics*; D001646:Bile / Q000737:chemistry / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D024841:Fluoroquinolones; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008828:Microbiological Techniques; D015363:Quinolones; D011817:Rabbits
D042462:4-Quinolones; D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D015363:Quinolones; C054745:temafloxacin
Etude expérimentale de la disposition hépatique et de l'élimination biliaire de la témafloxacine. Arguments en faveur de la production de métabolites actifs par le foie de Lapin.