title: Pharmacokinetic and pharmacodynamic properties of metomidate in turbot (Scophthalmus maximus) and halibut (Hippoglossus hippoglossus).
abstract: Metomidate was administered to halibut (Hippoglossus hippoglossus) and turbot (Scophthalmus maximus) intravenously at a dose of 3 mg/kg bodyweight, as a bath treatment at a dose of 9 mg/L water for 5 min to study the disposition of metomidate, and as bath treatment (9 mg/L) for 10 min to study the absorption and effect of metomidate on respiration and balance/motor control. Additionally, turbot were given metomidate orally at a dose of 7 mg/kg. The studies were performed in seawater at a temperature of 10.3 +/- 0.4 degrees C (halibut) and 18.0 +/- 0.3 degrees C (turbot). Pharmacokinetic modeling of the data showed that metomidate had shorter elimination half-life and higher plasma concentrations in turbot compared with halibut, both species displaying a rapid uptake, distribution and excretion. Following intravenous administration, the volumes of distribution at steady state (Vd(ss)) were 0.21 L/kg (halibut) and 0.44 L/kg (turbot). Plasma clearances (Cl) were 0.099 L/h.kg in halibut and 0.26 L/h.kg in turbot and the elimination half-lives (t(1/2)lambdaz) were calculated to be 5.8 h and 2.2 h in halibut and turbot, respectively. Mean residence times (MRT) were 2.2 h in halibut and 1.7 h in turbot. Following oral administration, the t(1/2)lambdaz was 3.5 h in turbot. The maximum plasma concentration (Cmax) was 7.8 mg/L in turbot 1 h after administration. The oral bioavailability (F) was calculated to 100% in turbot. Following 5 min bath the maximum plasma concentrations (Cmax), which were observed immediately after end of the bath, were 9.5 mg/L and 13.3 mg/L in halibut and turbot, respectively. Metomidate rapidly immobilized the fish, with respiratory depression, reduced heart rate, and loss of balance/motor control within 1 min (mean). Recovery was slow, with resumed balance/motor control after 26.4 min. Opercular respiration movements were resumed more rapidly with a recorded mean of 1.7 min. Oral administration was demonstrated to be a way of immobilizing fish, for example in large aquariums, without exposing them to unwanted stress.
authors.affiliation: Department of Pharmacology, Microbiology and Food Hygiene, Norwegian School of Veterinary Science, Oslo, Norway. Magne.Hansen@veths.no
authors.forename: M K
authors.initials: MK
authors.lastname: Hansen
authors.forename: U
authors.initials: U
authors.lastname: Nymoen
authors.forename: T E
authors.initials: TE
authors.lastname: Horsberg
mesh_terms: D000284:Administration, Oral; D000777:Anesthetics / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000818:Animals; D001682:Biological Availability; D005045:Etomidate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D005412:Flatfishes / Q000378:metabolism*; D005432:Flounder / Q000378:metabolism; D007101:Immersion; D007275:Injections, Intravenous / Q000662:veterinary; D009043:Motor Activity / Q000187:drug effects; D012869:Skin Absorption; D013045:Species Specificity
chemical_list: D000777:Anesthetics; C084586:metomidate; D005045:Etomidate