Pharmacokinetics, bioavailability and absorption of flumequine in the rat.
The study demonstrates that the oral extent of bioavailability of flumequine in the rat, relative to the intravenous injection, is complete (0.94 +/- 0.04) and not significantly different from that found by the intraduodenal route (0.95 +/- 0.04). The rate of oral bioavailability, however, is slow (ka = 1.20 +/- 0.07 h-1; Tmax = 2.0 h), but enough to maintain plasma levels above the minimal inhibitory concentration of the most common pathogens for an extended period of time (about 10 h). The reason for the oral absorption slowness could be a slow gastric emptying, an adsorption to the gastric mucosae, a precipitation in the gastric medium or any other feature concerning the stomach as the intraduodenal administration is very quick (kid = 38.1 +/- 4.7 h-1; Tmax = 0.05 h). A possible precipitation of flumequine cannot be discarded as the solubility of flumequine is very low in the pH range of 3 to 6 (mean pH values for rat stomach and rat intestine, respectively; T.T. Kararli, Biopharm. Drug Dispos. 16 (1995) 351-380). Flumequine was shown to be not substantially excreted in bile (2-3% of the dose). Surprisingly, plasma levels and AUC values found for animals with interrupted bile flow always surpass those found for animals with enterohepatic circulation. This could be due to experimental model features, which might bias plasmatic flumequine concentrations if the homeostatic equilibrium of the animal is not completely restored due to the volume reduction induced by biliary extraction.
Ruiz-García
A
A
Department of Pharmacy and Pharmaceutics, Faculty of Pharmacy, University of Valencia, Spain.
Bermejo
M
M
Merino
V
V
Sánchez-Castaño
G
G
Freixas
J
J
Garrigues
T M
TM
D000284:Administration, Oral; D000818:Animals; D000890:Anti-Infective Agents / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D004386:Duodenum / Q000378:metabolism; D004764:Enterohepatic Circulation / Q000502:physiology; D024841:Fluoroquinolones; D007408:Intestinal Absorption; D008297:Male; D008954:Models, Biological; D011807:Quinolizines / Q000097:blood / Q000493:pharmacokinetics*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D011807:Quinolizines; C012976:flumequine