Pharmacokinetic and pharmacodynamic analysis comparing diverse effects of detomidine, medetomidine, and dexmedetomidine in the horse: a population analysis

Abstract

The present study characterizes the pharmacokinetic (PK) and pharmacodynamic (PD) relationships of the α2-adrenergic receptor agonists detomidine (DET), medetomidine (MED) and dexmedetomidine (DEX) in parallel groups of horses from in vivo data after single bolus doses. Head height (HH), heart rate (HR), and blood glucose concentrations were measured over 6 h. Compartmental PK and minimal physiologically based PK (mPBPK) models were applied and incorporated into basic and extended indirect response models (IRM). Population PK/PD analysis was conducted using the Monolix software implementing the stochastic approximation expectation maximization algorithm. Marked reductions in HH and HR were found. The drug concentrations required to obtain inhibition at half-maximal effect (IC50) were approximately four times larger for DET than MED and DEX for both HH and HR. These effects were not gender dependent. Medetomidine had a greater influence on the increase in glucose concentration than DEX. The developed models demonstrate the use of mechanistic and mPBPK/PD models for the analysis of clinically obtainable in vivo data.

Pharmacokinetics of detomidine following intravenous or oral-transmucosal administration and sedative effects of the oral-transmucosal treatment in dogs

“…3,18 This is supported by findings of increased duration of sedation, but not necessarily depth of sedation, reported with other α 2 -adrenergic receptor agonists. Currently at the authors' institutions, doses up to 5.0 mg/m 2 have been administered to aggressive or extremely anxious dogs with no adverse effects observed.…”

A Double-Blinded, Randomized Comparison of Medetomidine-Tiletamine-Zolazepam and Dexmedetomidine-Tiletamine-Zolazepam Anesthesia in Free-Ranging Brown Bears (Ursus Arctos)

“…Medetomidine has been shown to cause greater increases in serum glucose concentration than D [25]. Although the effects of alpha-2 adrenoceptor agonists on cortisol concentrations are controversial [26, 27], we hypothesized that serum concentrations of cortisol, as an indicator of stress, would be less with DTZ.…”

Is there a place for dexmedetomidine in equine anaesthesia and analgesia? A systematic review (2005–2017)

“…Grimsrud et al. () compared the PK using a two‐compartment model by LC‐MS, with further PK/PD modelling of i.v. detomidine (30 μg/kg), medetomidine (10 μg/kg) and dexmedetomidine (5 μg/kg), reporting the drug concentration‐effect data.…”