title: Pharmacokinetics of flumequine and in vitro activity against bacterial pathogens of gilthead sea bream Sparus aurata.
abstract: The present study investigated the kinetic profile of flumequine (FLU) in gilthead sea bream Sparus aurata (170 g) held at 19 degrees C and evaluated its in vitro efficacy against important bacterial diseases in Mediterranean mariculture. Following a single intravascular injection (10 mg kg(-1) fish), the distribution half-life (t1/2alpha) and the half-life of the terminal phase of elimination (t1/2gamma) of the drug were 0.2 and 30 h respectively. Tissue penetration of FLU was low, since both the apparent distribution volume of the drug at steady-state (Vd(SS)) and the apparent volume of the central compartment (Vc) were small (0.57 and 0.15 l kg(-1)). The mean residence time (MRT) was short (11 h) and the total clearance (CL(T)) of the drug was slow (0.05 l kg(-1) h(-1)). Following oral administration (20 mg kg(-1)), the bioavailability (F %) of FLU was 29% and the maximum plasma concentration was 1.7 microg ml(-1). The minimum inhibitory concentration (MIC) of the drug in distilled water supplemented with 2% NaCl against Vibrio anguillarum Serotype 1b, Photobacterium damsela ssp. piscicida, V. alginolyticus, V. damsela and V. fluvialis was 0.15, 0.3, 1.2, 0.019 and 0.15 microg ml(-1) respectively. The addition however of 10 mM Ca2+ and 55 mM Mg2+ to the medium resulted in an 8- to >120-fold reduction in FLU activity. The results indicate that FLU has an adequate kinetic profile in gilthead sea bream and that marine cations induce a significant impact on the activity of FLU, rendering its use against bacterial pathogens questionable.
authors.affiliation: Laboratory of Fish Nutrition and Pathology, National Centre for Marine Research, Aghios Kosmas 16604, Ellinikon, Attiki, Greece. grigos@ncmr.gr
authors.forename: George
authors.initials: G
authors.lastname: Rigos
authors.forename: Athanassios E
authors.initials: AE
authors.lastname: Tyrpenou
authors.forename: Ioannis
authors.initials: I
authors.lastname: Nengas
authors.forename: Maria
authors.initials: M
authors.lastname: Yiagnisis
authors.forename: Maria
authors.initials: M
authors.lastname: Koutsodimou
authors.forename: Maria
authors.initials: M
authors.lastname: Alexis
authors.forename: Gera M
authors.initials: GM
authors.lastname: Troisi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D017756:Aquaculture; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D005393:Fish Diseases / Q000188:drug therapy / Q000382:microbiology; D024841:Fluoroquinolones; D007275:Injections, Intravenous / Q000662:veterinary; D008826:Microbial Sensitivity Tests / Q000662:veterinary; D010776:Photobacterium / Q000187:drug effects* / Q000254:growth & development; D011807:Quinolizines / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D021541:Sea Bream / Q000378:metabolism*; D014018:Tissue Distribution; D016896:Treatment Outcome; D014733:Vibrio / Q000187:drug effects* / Q000254:growth & development; D014735:Vibrio Infections / Q000188:drug therapy / Q000382:microbiology / Q000662:veterinary
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D011807:Quinolizines; C012976:flumequine