M Yata1, A J McLachlan2, D J R Foster3, A S Hanzlicek4, N J Beijerink5. 1. The University of Sydney, Faculty of Veterinary Science, University Veterinary Teaching Hospital Sydney, 65 Parramatta Road, Camperdown, NSW 2050, Australia. 2. The University of Sydney, Faculty of Pharmacy, A15 Pharmacy and Bank Building, University of Sydney, Sydney, NSW 2006, Australia. 3. 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. 4. Department of Veterinary Clinical Sciences, Oklahoma State University, Stillwater, OK 74078, USA. 5. 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.
Abstract
INTRODUCTION: To investigate the pharmacokinetics and pharmacodynamics of oral pimobendan in conscious, healthy cats. ANIMALS: Eight healthy adult cats. MATERIALS AND 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 t1/2 0.8 h vs. ODMP t1/2 1.6 h [LD]; pimobendan t1/2 0.7 h vs. ODMP t1/2 1.3 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.
INTRODUCTION: To investigate the pharmacokinetics and pharmacodynamics of oral pimobendan in conscious, healthy cats. ANIMALS: Eight healthy adult cats. MATERIALS AND 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 t1/2 0.8 h vs. ODMP t1/2 1.6 h [LD]; pimobendan t1/2 0.7 h vs. ODMP t1/2 1.3 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.
Authors: Karsten E Schober; John E Rush; Virginia Luis Fuentes; Tony Glaus; Nuala J Summerfield; Kathy Wright; Linda Lehmkuhl; Gerhard Wess; Margaret P Sayer; Joao Loureiro; John MacGregor; Nicole Mohren Journal: J Vet Intern Med Date: 2021-02-05 Impact factor: 3.333
Authors: Jessica L Ward; Efrem Z Kussin; Melissa A Tropf; Sandra P Tou; Teresa C DeFrancesco; Bruce W Keene Journal: J Vet Intern Med Date: 2020-10-07 Impact factor: 3.333
Authors: Maureen S Oldach; Yu Ueda; Eric S Ontiveros; Samantha L Fousse; Lance C Visser; Joshua A Stern Journal: BMC Vet Res Date: 2021-02-23 Impact factor: 2.741
Authors: Samantha L Kochie; Karsten E Schober; Jaylyn Rhinehart; Randolph L Winter; John D Bonagura; Annie Showers; Vedat Yildez Journal: J Vet Intern Med Date: 2020-11-26 Impact factor: 3.175