Pharmacokinetic and pharmacodynamic properties of metomidate in turbot ( Scophthalmus maximus) and halibut ( Hippoglossus hippoglossus)

• Published in: Journal of Veterinary Pharmacology and Therapeutics
• Main Authors: Hansen, M. K., Nymoen, U., Horsberg, T. E.
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wiley 2003
• Subjects: Scophthalmus maximus; Turbot
• Online Access: http://dx.doi.org/10.1046/j.1365-2885.2003.00454.x; https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1046%2Fj.1365-2885.2003.00454.x; https://onlinelibrary.wiley.com/doi/pdf/10.1046/j.1365-2885.2003.00454.x

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 °C (halibut) and 18.0 ± 0.3 °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 ( V d(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 ½ λ z ) 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 ½ λ z was 3.5 h in turbot. The maximum plasma concentration ( C max ) 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 ( C max ), 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 ...