Single-dose pharmacokinetics and cardiovascular effects of oral pimobendan in healthy cats

Yata, M.; McLachlan, Andrew J.; Foster, David J. R.; Hanzlicek, Andrew S; Beijerink, Niek

doi:10.1016/j.jvc.2016.07.001

Cited by 23 publications

(42 citation statements)

References 45 publications

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“…Similar to a previous study, we did not identify any observable increase in systolic function at our single time point evaluation (21). In order to identify any impact on systolic function, the prior study averaged effects over multiple evaluations 12 h post-pimobendan administration (20).…”

Section: Discussionsupporting

confidence: 89%

“…The study was limited by the fact that the time to peak physiologic drug effects of pimobendan in cats remains unknown (21). Although the time to peak plasma concentration has been identified and was used in this study as a surrogate for peak physiologic effect, the peak plasma concentration does not necessarily correlate with peak drug effects.…”

Section: Discussionmentioning

confidence: 99%

“…Pimobendan has also been shown to decrease left atrial (LA) size in normal cats, implying some lusitropic or LA function benefit (20). These pharmacodynamic qualities of the drug may represent the source of benefit for cats with HCM and CHF, but to date, although many studies have documented that pimobendan is well-tolerated in cats, there have been no studies evaluating the pharmacodynamics of pimobendan in cats with HCM (14, 21–26). Thus, it remains unknown whether pimobendan could induce or exacerbate dynamic LVOTOs, and whether any positive effects can be documented in cats with HCM.…”

Section: Introductionmentioning

confidence: 99%

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Cardiac Effects of a Single Dose of Pimobendan in Cats With Hypertrophic Cardiomyopathy; A Randomized, Placebo-Controlled, Crossover Study

et al. 2019

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Background: Pimobendan has been shown to impart a significant survival benefit in cardiomyopathic cats who receive it as part of heart failure therapy. However, use of pimobendan remains controversial in cats with hypertrophic cardiomyopathy (HCM) due to lack of pharmacodynamic data for pimobendan in cats with HCM and due to theoretical concerns for exacerbating left ventricular outflow tract obstructions.Hypothesis/Objectives: Our objective was to investigate the cardiac effects of pimobendan in cats with HCM. We hypothesized that pimobendan would not exacerbate left ventricular outflow tract obstructions and that it would improve echocardiographic measures of diastolic function.Animals: Thirteen purpose-bred cats were studied from a research colony with naturally-occurring HCM due to a variant in myosin binding protein C.Methods: Cats underwent two examinations 24 h apart with complete standard echocardiography. On their first day of evaluation, they were randomized to receive oral placebo or 1.25 mg pimobendan 1 h prior to exam. On their second examination, they were crossed over and received the remaining treatment. Investigators were blinded to all treatments.Results: The pimobendan group had a significant increase in left atrial fractional shortening (pimobendan group 41.7% ± 5.9; placebo group 36.1% ± 6.0; p = 0.04). There was no significant difference in left ventricular outflow tract (LVOT) velocities between the groups (pimobendan group 2.8 m/s ± 0.8; placebo group 2.6 m/s ± 1.0). There were no significant differences between the number of cats with LVOT obstructions between groups (12 in pimobendan group; 11 in placebo group; p = 1.00). There were no detectable differences in any systolic measures, including left ventricular fractional shortening, mitral annular plane systolic excursion, and tricuspid annular plane systolic excursion. Doppler-based diastolic function assessment was precluded by persistent tachycardia.Conclusions: Improved left atrial function in the pimobendan group could explain some of the reported survival benefit for HCM cats in CHF. Pimobendan did not exacerbate LVOT obstructions and thus may not be contraindicated in HCM cats with LVOT obstructions. Future studies are needed to better characterize other physiologic effects, particularly regarding diastolic function assessment, and to better assess safety of pimobendan over a longer time-course.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cardiac Effects of a Single Dose of Pimobendan in Cats With Hypertrophic Cardiomyopathy; A Randomized, Placebo-Controlled, Crossover Study

et al. 2019

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“…Therefore, ODMP is active and may have an important contribution to the hemodynamic effects of pimobendan. However, there is sparse data regarding the pharmacokinetic profile of ODMP in dogs (26). The manufacturer's package insert reported that pimobendan 0.25 mg/kg PO resulted in an ODMP C max of 3.66 ± 1.21 with T max at 2 h (15).…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Pimobendan and Its Metabolite O-Desmethyl-Pimobendan Following Rectal Administration to Healthy Dogs

et al. 2020

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This study describes the pharmacokinetics of parent pimobendan (PIM) and its active metabolite, o-desmethyl-pimobendan (ODMP), after oral and rectal administration of pimobendan to healthy dogs. Animals: A total of eight healthy privately owned dogs were used in this study. Procedures: The dogs received a single dose (0.5 mg/kg) of a commercially available pimobendan tablet per os (PO). Twelve blood samples were collected over a 12-h period for pharmacokinetic analysis. After a 24-h washout period, the dogs received the same dose of pimobendan solution per rectum (PR), and samples were obtained at the same time for analysis. Results: For PIM, PO vs. PR, respectively, the mean maximum plasma concentration (C max , ng/ml) was 49.1 ± 28.7 vs. 10.1 ± 2, the time to reach a maximum concentration (T max , h) was 2.1 ± 0.9 vs. 1 ± 0.4, the disappearance half-life (t 1/2 , h) was 1.8 ± 0.8 vs. 2.2 ± 0.6, and the area under the concentration-time curve (AUC, ng * h/ml) was 148.4

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“…(0.25-0.3 mg/kg PO q12h; total daily dose 0.5-0.6 mg/kg/day). Pharmacokinetic studies of pimobendan in healthy cats have demonstrated that pimobendan has a substantially higher maximal drug plasma concentration and longer elimination half-life in cats compared to dogs,25 but decreased conversion to the active metabolite Odesmethylpimobendan 26. Therefore, although the ideal dose of pimobendan in cats remains unknown, the use of the canine dose seems rational given the existing pharmacokinetic and pharmacodynamics data.…”

mentioning

confidence: 99%

Retrospective evaluation of the safety and tolerability of pimobendan in cats with obstructive vs nonobstructive cardiomyopathy

Ward

Kussin

Tropf

et al. 2020

Veterinary Internal Medicne

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Background: Pimobendan is frequently used off-label for treatments of cats with congestive heart failure (CHF). Concern exists regarding the safety of pimobendan in cats with outflow tract obstruction (OTO). Objectives: In cats treated with pimobendan, incidence of adverse effects will not differ between cats with OTO vs cats with nonobstructive cardiomyopathy. Animals: Two-hundred sixty cats with CHF (57 with OTO, 203 with nonobstructive disease). Methods: Retrospective medical record review. Groups were compared using 2-sample t-tests, Wilcoxon rank-sum tests, and Fisher exact tests.

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Single-dose pharmacokinetics and cardiovascular effects of oral pimobendan in healthy cats

Cited by 23 publications

References 45 publications

Cardiac Effects of a Single Dose of Pimobendan in Cats With Hypertrophic Cardiomyopathy; A Randomized, Placebo-Controlled, Crossover Study

Cardiac Effects of a Single Dose of Pimobendan in Cats With Hypertrophic Cardiomyopathy; A Randomized, Placebo-Controlled, Crossover Study

Pharmacokinetics of Pimobendan and Its Metabolite O-Desmethyl-Pimobendan Following Rectal Administration to Healthy Dogs

Retrospective evaluation of the safety and tolerability of pimobendan in cats with obstructive vs nonobstructive cardiomyopathy

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