Pimobendan

Pimobendan is a selective inhibitor of PDE3 with IC50 of 0.32 μM.

Pimobendan in Chronic Right Heart Failure in a Left Ventricular Assist Device Patient.[Pubmed:28018821]

Thorac Cardiovasc Surg Rep. 2016 Dec;5(1):39-40.

We report the case of a 76-year-old patient who developed chronic right heart failure 1 year after left ventricular assist device implantation due to ischemic cardiomyopathy. Initial recompensation was achieved through dobutamin, sildenafil, and levosimendan treatment. Yet, discharge was successful only after the off-label use of the oral calcium sensitizer Pimobendan. Ten months after discharge, the patient presents with no clinical signs of right heart failure and significantly improved right heart function without any impairment in quality of life.

Efficacy of pimobendan on survival and reoccurrence of pulmonary edema in canine congestive heart failure.[Pubmed:27644192]

J Vet Med Sci. 2017 Jan 20;79(1):29-34.

The aim of this study was to evaluate the efficacy of Pimobendan with conventional therapies on survival and reocurrence of pulmonary edema in dogs with congestive heart failure (CHF) caused by myxomatous mitral valve disease (MMVD). Records of 197 client-owned dogs from 14 veterinary hospitals were included in this study. Dogs were administered conventional treatments with or without Pimobendan. Sixty-four dogs received a standard dose of Pimobendan (0.20-0.48 mg/kg every 12 hr (q12hr)), 49 dogs received a low dose of Pimobendan (0.05-0.19 mg/kg q12hr), and 84 dogs received conventional therapy alone. Dogs in the standard-dose and low-dose Pimobendan groups had significantly longer median survival times than dogs in the conventional group (334, 277 and 136 days, respectively; P<0.001). The reoccurrence rate of pulmonary edema in the standard-dose group was significantly lower than in the low-dose and conventional groups (43%, 59% and 62%, respectively; P<0.05). Combination of Pimobendan with a conventional treatment regimen significantly prolonged survival time after an initial episode of pulmonary edema in dogs with CHF caused by MMVD. There was no difference in survival between dogs administered standard and low doses of Pimobendan, but Pimobendan did prevent the reoccurrence of pulmonary edema in a dose-dependent manner.

Single-dose pharmacokinetics and cardiovascular effects of oral pimobendan in healthy cats.[Pubmed:27613648]

J Vet Cardiol. 2016 Dec;18(4):310-325.

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-infinity greater than ODMP AUC0-infinity (ODMP:Pimobendan AUC0-infinity 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-infinity 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.

Effect of Pimobendan in Dogs with Preclinical Myxomatous Mitral Valve Disease and Cardiomegaly: The EPIC Study-A Randomized Clinical Trial.[Pubmed:27678080]

J Vet Intern Med. 2016 Nov;30(6):1765-1779.

BACKGROUND: Pimobendan is effective in treatment of dogs with congestive heart failure (CHF) secondary to myxomatous mitral valve disease (MMVD). Its effect on dogs before the onset of CHF is unknown. HYPOTHESIS/OBJECTIVES: Administration of Pimobendan (0.4-0.6 mg/kg/d in divided doses) to dogs with increased heart size secondary to preclinical MMVD, not receiving other cardiovascular medications, will delay the onset of signs of CHF, cardiac-related death, or euthanasia. ANIMALS: 360 client-owned dogs with MMVD with left atrial-to-aortic ratio >/=1.6, normalized left ventricular internal diameter in diastole >/=1.7, and vertebral heart sum >10.5. METHODS: Prospective, randomized, placebo-controlled, blinded, multicenter clinical trial. Primary outcome variable was time to a composite of the onset of CHF, cardiac-related death, or euthanasia. RESULTS: Median time to primary endpoint was 1228 days (95% CI: 856-NA) in the Pimobendan group and 766 days (95% CI: 667-875) in the placebo group (P = .0038). Hazard ratio for the Pimobendan group was 0.64 (95% CI: 0.47-0.87) compared with the placebo group. The benefit persisted after adjustment for other variables. Adverse events were not different between treatment groups. Dogs in the Pimobendan group lived longer (median survival time was 1059 days (95% CI: 952-NA) in the Pimobendan group and 902 days (95% CI: 747-1061) in the placebo group) (P = .012). CONCLUSIONS AND CLINICAL IMPORTANCE: Administration of Pimobendan to dogs with MMVD and echocardiographic and radiographic evidence of cardiomegaly results in prolongation of preclinical period and is safe and well tolerated. Prolongation of preclinical period by approximately 15 months represents substantial clinical benefit.