Pharmacokinetics of intramuscular alfaxalone and its echocardiographic, cardiopulmonary and sedative effects in healthy dogs.

Autor: Cruz-Benedetti IC; Université de Lyon, VetAgro Sup, GREAT, Marcy l'Etoile, France., Bublot I; Université de Lyon, VetAgro Sup, Unit of Cardiology, Marcy l'Etoile, France., Ribas T; Azurvet, Hippodrome, Cagnes sur mer, France., Fourel I; Université de Lyon, VetAgro Sup, INRA, USC1233, RS2GP, Marcy l'Etoile, France., Vogl C; Department of Animal Husbandry and Genetics, Section for Molecular Biology, Vetmeduni, Vienna, Austria., Dubois C; Université de Lyon, VetAgro Sup, GREAT, Marcy l'Etoile, France., Milani M; Université de Lyon, VetAgro Sup, Unit of Cardiology, Marcy l'Etoile, France., Ida KK; Université de Lyon, VetAgro Sup, GREAT, Marcy l'Etoile, France.; Laboratory of Medical Investigation 8, Anaesthesiology, Medical School, University of São Paulo, São Paulo, Brazil., Portier K; Université de Lyon, VetAgro Sup, GREAT, Marcy l'Etoile, France.; Univ Lyon, CarMeN Laboratory, INSERM, INRA, INSA Lyon, Université Claude Bernard Lyon 1, Bron, France.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2018 Sep 24; Vol. 13 (9), pp. e0204553. Date of Electronic Publication: 2018 Sep 24 (Print Publication: 2018).
DOI: 10.1371/journal.pone.0204553
Abstrakt: The pharmacokinetics and the effects of a single intramuscular (IM) dose of alfaxalone on sedation and cardiopulmonary and echocardiographic variables was studied in dogs. Twelve healthy adult Beagles (3 females, 9 males) were used in this prospective controlled cross-over trial. Echocardiography was performed with and without 4 mg kg-1 alfaxalone IM with a week wash-out interval. Sedation (19-point scale; 0 = no sedation), cardiopulmonary parameters, blood gas analysis and plasma concentration of alfaxalone were assessed every 5 minutes following the injection (T0). The influence of the alfaxalone plasma concentration and time on physiological variables was tested using a linear model whereas echocardiographic measurements were compared between conscious and alfaxalone-administered dogs using paired t-tests. Compared to baseline, alfaxalone administration was followed by an increase in heart rate (HR) from T5 to T30 and a decrease in mean arterial pressure (MAP) at T10, T25 and T30, in stroke volume (SV; 15 ± 5 to 11 ± 3 ml; P<0.0001), and end-diastolic volume (EDV; 24.7 ± 5.7 to 19.4 ± 4.9 ml). Cardiac output (CO) and blood gas analysis did not change significantly throughout. Mean plasma half-life was 29 ± 8 minutes, volume of distribution was 1.94 ± 0.63 L kg-1, and plasma clearance was 47.7 ± 14.1 ml kg-1 minute-1. Moderate to deep sedation was observed from T5 to T35. Ten dogs showed paddling, trembling, nystagmus and strong reaction to sound during the procedure. Although there were no significant changes in CO and oxygenation, the impact of HR, MAP, SV, EDV alterations requires further investigations in dogs with cardiac disease.
Competing Interests: The authors have declared no competing interests exist. Dr Bublot and Dr Milani were employed by VetAgro Sup during the study. They are now working in private clinics. The addresses of these clinics have been added as "current adresses". This does not alter our adherence to PLOS ONE policies on sharing data and materials.
Databáze: MEDLINE
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