Single-dose pharmacokinetics and cardiovascular effects of oral pimobendan in healthy cats.
BACKGROUND
To investigate the pharmacokinetics and pharmacodynamics of oral pimobendan in conscious, healthy cats.


METHODS
Eight healthy adult cats.


METHODS
A randomised, single-blinded, crossover design was used. Two oral doses of pimobendan (0.625-mg [LD], 1.25-mg [HD]) and a control substance (3-mL water) were administered to each cat. Blood collection, echocardiography, and oscillometric blood pressure measurements were performed repeatedly for 12 h following each dose. Plasma concentrations of pimobendan and the active metabolite, O-desmethylpimobendan (ODMP), were quantified using ultra-high-performance liquid chromatography tandem mass spectrometry. Cardiovascular parameters were evaluated for between- and within-treatment effects over time using linear mixed modelling.


RESULTS
Pimobendan was rapidly absorbed and converted to ODMP with the pimobendan AUC0-∞greater than ODMP AUC0-∞(ODMP:pimobendan AUC0-∞ratio 0.6 [LD] and 0.5 [HD]) despite a longer elimination half-life of ODMP (pimobendan t1/20.8 h vs. ODMP t1/21.6 h [LD]; pimobendan t1/20.7 h vs. ODMP t1/21.3 h [HD]). Averaged across all time points, pimobendan increased several measures of systolic function; however, its effect could not be further characterised. Although treatment was well-tolerated, two cats vomited following HD and another had a ventricular premature beat recorded following LD.


CONCLUSIONS
The lower ODMP:pimobendan AUC0-∞ratio compared to that observed previously in dogs suggests reduced metabolism in cats. Treatment effects were observed in measures of systolic function; however, the duration of action and differences in effects between the two pimobendan doses could not be characterised. Further studies are required to evaluate pimobendan in feline cardiovascular medicine.
The University of Sydney, Faculty of Veterinary Science, University Veterinary Teaching Hospital Sydney, 65 Parramatta Road, Camperdown, NSW 2050, Australia.
M
M
Yata
The University of Sydney, Faculty of Pharmacy, A15 Pharmacy and Bank Building, University of Sydney, Sydney, NSW 2006, Australia.
A J
AJ
McLachlan
Australian Centre for Pharmacometrics, School of Pharmacy and Medical Sciences, University of South Australia, Division of Health Sciences, GPO Box 2471, Adelaide, SA 5001, Australia; Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Division of Health Sciences, GPO Box 2471, Adelaide, SA 5001, Australia.
D J R
DJ
Foster
Department of Veterinary Clinical Sciences, Oklahoma State University, Stillwater, OK 74078, USA.
A S
AS
Hanzlicek
The University of Sydney, Faculty of Veterinary Science, University Veterinary Teaching Hospital Sydney, 65 Parramatta Road, Camperdown, NSW 2050, Australia. Electronic address: niek.beijerink@sydney.edu.au.
N J
NJ
Beijerink
D000284:Administration, Oral; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D002319:Cardiovascular System / Q000187:drug effects*; D002415:Cats; D018592:Cross-Over Studies; D004452:Echocardiography / Q000662:veterinary; D005260:Female; D008297:Male; D015588:Observer Variation; D011724:Pyridazines / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology; D016037:Single-Blind Method
D002316:Cardiotonic Agents; C000618656:O-desmethylpimobendan; D011724:Pyridazines; C041648:pimobendan
Feline; Inodilator; Metabolite pharmacokinetics; Pharmacodynamics; UD-CG 212