Pharmacokinetics of flumequine and in vitro activity against bacterial pathogens of gilthead sea bream Sparus aurata.
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.
Rigos
George
G
Laboratory of Fish Nutrition and Pathology, National Centre for Marine Research, Aghios Kosmas 16604, Ellinikon, Attiki, Greece. grigos@ncmr.gr
Tyrpenou
Athanassios E
AE
Nengas
Ioannis
I
Yiagnisis
Maria
M
Koutsodimou
Maria
M
Alexis
Maria
M
Troisi
Gera M
GM
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
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D011807:Quinolizines; C012976:flumequine