Kallio-Kujala , I J , Raekallio , M R , Honkavaara , J , Bennett , R C , Turunen , H , Scheinin , M , Hautajärvi , H & Vainio , O 2018 , ' Peripheral α 2 -adrenoceptor antagonism affects the absorption of intramuscularly coadministered drugs ' , Veterinary Anaesthesia and Analgesia , vol. 45 , no. 4 , pp. 405-413 . https://doi.org/10.1016/j.vaa.2018.01.008
Title: | Peripheral α2-adrenoceptor antagonism affects the absorption of intramuscularly coadministered drugs |
Author: | Kallio-Kujala, Ira J.; Raekallio, Marja R.; Honkavaara, Juhana; Bennett, Rachel C.; Turunen, Heta; Scheinin, Mika; Hautajärvi, Heidi; Vainio, Outi |
Contributor organization: | Equine and Small Animal Medicine Departments of Faculty of Veterinary Medicine Faculty of Veterinary Medicine Marja Raekallio / Principal Investigator Outi Vainio / Principal Investigator Research Centre for Animal Welfare DAPHNE - Developing Assessment Practices in Higher Education Teachers' Academy |
Date: | 2018-07 |
Language: | eng |
Number of pages: | 9 |
Belongs to series: | Veterinary Anaesthesia and Analgesia |
ISSN: | 1467-2987 |
DOI: | https://doi.org/10.1016/j.vaa.2018.01.008 |
URI: | http://hdl.handle.net/10138/298627 |
Abstract: | Objective: We determined the possible effects of a peripherally acting alpha2-adrenoceptor antagonist, MK-467, on the absorption of intramuscularly (IM) co-administered medetomidine, butorphanol and midazolam. Study design: Randomized, experimental, blinded cross-over study. Animals: Six healthy Beagle dogs. Methods: Two IM treatments were administered: 1) medetomidine hydrochloride (20 μg kg-1) + butorphanol (100 μg kg-1) + midazolam (200 μg kg-1) (MBM), and; 2) MBM + MK-467 hydrochloride (500 μg kg-1) (MBM-MK), mixed in a syringe. Heart rate was recorded at regular intervals. Sedation was assessed with visual analog scales (0 – 100 mm). Drug concentrations in plasma were analyzed with liquid chromatography - tandem mass spectrometry, with chiral separation of dex- and levomedetomidine. Maximum drug concentrations in plasma (Cmax) and time to Cmax (Tmax) were determined. Paired t-tests, with Bonferroni correction when appropriate, were used for comparisons between the treatments. Results: Data from five dogs were analyzed. Heart rate was significantly higher from 20 until 90 minutes after MBM-MK. The Tmax for midazolam and levomedetomidine (mean ± standard deviation) were approximately halved with co-administration of MK-467, from 23 ± 9 to 11 ± 6 minutes (p = 0.049) for midazolam and from 32 ± 15 to 18 ± 6 minutes for levomedetomidine (p = 0.036), respectively. Conclusions and clinical relevance: MK-467 accelerated the absorption of IM co-administered drugs. This is clinically relevant as it may hasten the onset of peak sedative effects. |
Subject: |
alpha(2)-agonist
dog intramuscular medetomidine MK-467 peripheral alpha(2)-antagonist CONSCIOUS DOGS ALPHA-2-ADRENOCEPTOR ANTAGONIST INTRAVENOUS DEXMEDETOMIDINE RECEPTOR ANTAGONIST MEDETOMIDINE PHARMACOKINETICS CARDIOPULMONARY COMBINATION SEDATION 413 Veterinary science |
Peer reviewed: | Yes |
Rights: | cc_by_nc_nd |
Usage restriction: | openAccess |
Self-archived version: | acceptedVersion |
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