Disposition, behavioural and physiological effects of escalating doses of intravenously administered fentanyl to young foals

Summary Reasons for performing study Foal responses to a broader range of plasma fentanyl concentrations than currently reported are desirable to support (or not) clinical use. Objectives To describe fentanyl plasma concentrations following an escalating i.v. fentanyl dosing schedule in foals aged 5–13 days and describe selected, associated dose‐ and time‐related behavioural and physiological responses to plasma fentanyl concentration. Study design Experimental. Methods Fentanyl was administered i.v. in an escalating fashion (2, 4, 8, 16 and 32 μg/kg bwt) at 10‐min intervals. Blood samples were collected before and at selected times until 24 h post administration. Blood samples were analysed for fentanyl and metabolite concentrations and correlated with behavioural and physiological observations and selected blood analytes. Results Foals mostly appeared to be unaffected following 2 μg/kg bwt (1.09 ± 0.41 μg/l; average maximal plasma concentration) of fentanyl, but 6 of the 8 foals appeared to be sedated following 4 μg/kg bwt (3.07 ± 1.11 μg/l). Ataxia with increased locomotor activity, muscle rigidity and head pressing posture was observed in many foals at 8 (7.24 ± 3.22 μg/l) and 16 μg/kg bwt (17.4 ± 5.67 μg/l). All foals were heavily sedated after 32 μg/kg bwt (34.5 ± 10.3 μg/l); 3 of the 8 foals became recumbent. The average (± s.d.) terminal half‐life following administration of the final dose was 44.2 ± 9.85 min. Conclusions Behavioural and physiological responses to i.v. fentanyl in young foals are dose related. As with mature horses, the window of fentanyl plasma concentrations related to possible clinically desirable actions appears relatively narrow.