Peripheral α2-adrenoceptor antagonism affects the absorption of intramuscularly coadministered drugs.
Vet Anaesth Analg
; 45(4): 405-413, 2018 Jul.
Article
em En
| MEDLINE
| ID: mdl-29891212
ABSTRACT
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. STUDYDESIGN:
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Quinolizinas
/
Midazolam
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Butorfanol
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Medetomidina
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Antagonistas de Receptores Adrenérgicos alfa 2
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Hipnóticos e Sedativos
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Injeções Intramusculares
Limite:
Animals
Idioma:
En
Revista:
Vet Anaesth Analg
Assunto da revista:
ANESTESIOLOGIA
/
MEDICINA VETERINARIA
Ano de publicação:
2018
Tipo de documento:
Article