A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä

Peripheral α2-adrenoceptor antagonism affects the absorption of intramuscularly coadministered drugs




TekijätIra J. Kallio-Kujala, Marja R. Raekallio, Juhana Honkavaara, Rachel C. Bennett, Heta Turunen, Mika Scheinin, Heidi Hautajärvi, Outi Vainio

KustantajaAssociation of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia

Julkaisuvuosi2018

JournalVeterinary Anaesthesia and Analgesia

Tietokannassa oleva lehden nimiVeterinary Anaesthesia and Analgesia

Vuosikerta45

Numero4

Aloitussivu405

Lopetussivu413

Sivujen määrä9

ISSN1467-2987

eISSN1467-2995

DOIhttps://doi.org/10.1016/j.vaa.2018.01.008


Tiivistelmä

Objective: We determined the possible effects of a peripherally acting α2-adrenoceptor antagonist, MK-467, on the absorption of intramuscularly (IM) coadministered medetomidine, butorphanol and midazolam.

Study design: Randomized, experimental, blinded crossover 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 to 90 minutes after MBM–MK. The Tmax values for midazolam and levomedetomidine (mean ± standard deviation) were approximately halved with coadministration 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 coadministered drugs. This is clinically relevant as it may hasten the onset of peak sedative effects.



Last updated on 2024-26-11 at 11:41