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1.
BACKGROUND: Despite traditional therapy of a diuretic, angiotensin converting enzyme inhibitor, digoxin, or a combination of these drugs, survival of dogs with dilated cardiomyopathy (DCM) is low. Pimobendan, an inodilator, has both inotropic and balanced peripheral vasodilatory properties. HYPOTHESIS: Pimobendan when added to conventional therapy will improve morbidity and reduce case fatality rate in Doberman Pinschers with congestive heart failure (CHF) caused by DCM. ANIMALS: Sixteen Doberman Pinschers in CHF caused by DCM. METHODS: A prospective randomized, double-blind, placebo-controlled study with treatment failure as the primary and quality of life (QoL) indices as secondary outcome variables. Therapy consisted of furosemide (per os [PO] as required) and benazepril hydrochloride (0.5 mg/kg PO q12h) and dogs were randomized in pairs and by sex to receive pimobendan (0.25 mg/kg PO q12h) or placebo (1 tablet PO q12h). RESULTS: Pimobendan-treated dogs had a significant improvement in time to treatment failure (pimobendan median, 130.5 days; placebo median, 14 days; P= .002; risk ratio = 0.35, P= .003, lower 5% confidence limit = 0.13, upper 95% confidence limit = 0.71). Number and rate of dogs reaching treatment failure in the placebo group precluded the analysis of QoL. CONCLUSIONS AND CLINICAL IMPORTANCE: Pimobendan should be used as a first-line therapeutic in Doberman Pinschers for the treatment of CHF caused by DCM.  相似文献   

2.

Background

Changes in clinical variables associated with the administration of pimobendan to dogs with preclinical myxomatous mitral valve disease (MMVD ) and cardiomegaly have not been described.

Objectives

To investigate the effect of pimobendan on clinical variables and the relationship between a change in heart size and the time to congestive heart failure (CHF ) or cardiac‐related death (CRD ) in dogs with MMVD and cardiomegaly. To determine whether pimobendan‐treated dogs differ from dogs receiving placebo at onset of CHF .

Animals

Three hundred and fifty‐four dogs with MMVD and cardiomegaly.

Materials and Methods

Prospective, blinded study with dogs randomized (ratio 1:1) to pimobendan (0.4–0.6 mg/kg/d) or placebo. Clinical, laboratory, and heart‐size variables in both groups were measured and compared at different time points (day 35 and onset of CHF ) and over the study duration. Relationships between short‐term changes in echocardiographic variables and time to CHF or CRD were explored.

Results

At day 35, heart size had reduced in the pimobendan group: median change in (Δ) LVIDDN ?0.06 (IQR : ?0.15 to +0.02), P  < 0.0001, and LA :Ao ?0.08 (IQR : ?0.23 to +0.03), P  < 0.0001. Reduction in heart size was associated with increased time to CHF or CRD . Hazard ratio for a 0.1 increase in ΔLVIDDN was 1.26, P  = 0.0003. Hazard ratio for a 0.1 increase in ΔLA :Ao was 1.14, P  = 0.0002. At onset of CHF , groups were similar.

Conclusions and Clinical Importance

Pimobendan treatment reduces heart size. Reduced heart size is associated with improved outcome. At the onset of CHF , dogs treated with pimobendan were indistinguishable from those receiving placebo.
  相似文献   

3.
Background: Spironolactone, an aldosterone antagonist, has been demonstrated to decrease mortality in human patients when added to other cardiac therapies. Hypothesis: Spironolactone in addition to conventional therapy increases survival compared with conventional therapy in dogs with naturally occurring myxomatous mitral valve disease (MMVD). Animals: Between February 2003 and March 2005, 221 dogs were recruited in Europe. Nine dogs were excluded from analysis, leaving 212 dogs with moderate to severe mitral regurgitation (MR) caused by MMVD (International Small Animal Cardiac Health Council classification classes II [n = 190] and III [n = 21]). Methods: Double‐blinded, field study conducted with dogs randomized to receive either spironolactone (2 mg/kg once a day) or placebo in addition to conventional therapy (angiotensin converting enzyme inhibitor, plus furosemide and digoxin if needed). Primary endpoint was a composite of cardiac‐related death, euthanasia, or severe worsening of MR. Results: Primary endpoint reached by 11/102 dogs (10.8%) in the spironolactone group (6 deaths, 5 worsening) versus 28/110 (25.5%) in control group (14 deaths, 8 euthanasia, 6 worsening). Risk of reaching the composite endpoint significantly decreased by 55% (hazard ratio [HR] = 0.45; 95% confidence limits [CL], 0.22–0.90; log rank test, P= .017). Risk of cardiac‐ related death or euthanasia significantly reduced by 69% (HR = 0.31; 95% CL, 0.13–0.76; P= .0071). Number of dogs not completing the study for cardiac and other miscellaneous reasons similar in spironolactone (67/102) and control groups (66/110). Conclusion and Clinical Importance: Spironolactone added to conventional cardiac therapy decreases the risk of reaching the primary endpoint (ie, cardiac‐related death, euthanasia, or severe worsening) in dogs with moderate to severe MR caused by MMVD.  相似文献   

4.
Pimobendan is a novel agent with properties that are highly desirable in the clinical management of congestive heart failure (CHF) secondary to both dilated cardiomyopathy (DCM) and chronic degenerative valvular disease in dogs. Review of available data suggests that pimobendan is safe, well tolerated, and leads to enhanced quality of life in dogs with CHF secondary to DCM or chronic valvular disease when used in combination with furosemide or other conventional therapies (e.g., angiotensin-converting enzyme inhibitors, digoxin). Pimobendan leads to a reduction in mortality from CHF associated with DCM, and ongoing studies are evaluating its effects on mortality associated with chronic valvular disease.  相似文献   

5.
A double-blind, randomized, placebo-controlled study was conducted to examine the effect on heart failure class and survival of pimobendan, an oral calcium-sensitizing inodilator, in dogs with dilated cardiomyopathy (DCM). Pimobendan (0.3-0.6 mg/kg body weight/d) or placebo was administered to English Cocker Spaniels (CSs; n = 10) and Doberman Pinschers (DPs: n = 10) that had DCM in addition to background therapy of furosemide, enalapril, and digoxin. Addition of pimobendan to standard triple therapy was associated with a significant improvement in heart failure class, regardless of breed (P < .02, Mann-Whitney rank sum test). Overall, 8 of 10 animals in the pimobendan-treated group, and 1 of 10 animals in the placebo group improved their heart failure status by at least I modified New York Heart Association functional class after initial stabilization (P = .005, Fisher's exact test). Pimobendan had no significant effect on survival in the CSs (P = 0.77, log-rank test), but DPs treated with pimobendan had significantly longer survival times compared with placebo (P < .02, log-rank test), with a median survival time of 329 days in the pimobendan group compared with 50 days in the placebo group, and a hazard ratio of 3.4 (95% confidence interval 1.4-39.8). Pimobendan resulted in significant improvement in heart failure class when added to standard therapy in this group of dogs with DCM, and may have contributed to improved survival in DPs.  相似文献   

6.
This retrospective study reports the survival time [onset of congestive heart failure (CHF) to death from any cause] of 21 dogs with mitral regurgitation (MR) and CHF treated with a combination of furosemide, angiotensin-converting enzyme inhibitor (ACEI, benazepril, or enalapril), pimobendan, spironolactone, and amlodipine. Baseline echocardiographic data: end-systolic and end-diastolic volume indices (ESVI and EDVI), left atrium to aorta ratio (LA/Ao), and regurgitant fraction (RF) are reported. Median survival time (MST) was 430 d. Initial dosage of furosemide (P = 0.0081) and LA/Ao (P = 0.042) were negatively associated with survival. Baseline echocardiographic indices (mean ± standard deviation) were 40.24 ± 16.76 for ESVI, 161.48 ± 44.49 mL/m(2) for EDVI, 2.11 ± 0.75 for LA/Ao, and 64.71 ± 16.85% for RF. Combining furosemide, ACEI, pimobendan, spironolactone, and amlodipine may result in long survival times in dogs with MR and CHF. Severity of MR at onset of CHF is at least moderate.  相似文献   

7.
Introduction/objectivesWhether the aldosterone antagonist spironolactone has beneficial survival effects in dogs with dilated cardiomyopathy (DCM) is not known. The primary objective of the study was to evaluate the effect of spironolactone, when added to conventional therapy, on survival time in Doberman pinschers with congestive heart failure (CHF) due to DCM.AnimalsSixty-seven client-owned Doberman pinschers with CHF due to DCM.Materials and methodsThe trial design was prospective, randomized, blinded, and placebo controlled. Dogs were randomized to receive 50–75 mg of spironolactone twice daily (n = 34) or a placebo (n = 33), in addition to standard CHF therapy. Follow-up visits were targeted every one–six weeks until endpoint. Quality-of-life questionnaire and physical examination were performed at every visit, while renal biochemistry, ECG, echocardiography, and thoracic radiography were reassessed as needed. The primary endpoint was time to cardiac death, defined as death or euthanasia from CHF or sudden death.ResultsMedian time to primary endpoint in the spironolactone group (183 days) was not statistically significantly different than that for the placebo group (124 days) (P = 0.254). The development of atrial fibrillation (AF) was significantly less frequent in the spironolactone group (n = 7) than the placebo group (n = 15, P = 0.037).ConclusionsWhile median time to cardiac death in the spironolactone group was not statistically significantly different than that in the placebo group, adding spironolactone to conventional therapy resulted in reduced occurrence of AF.  相似文献   

8.
Hypothesis/ObjectivesTo describe the therapeutic use of pimobendan in cats, describe the patient population to which it was administered, document potential side effects and report the clinical course following administration of pimobendan in conjunction with standard heart failure therapy. It is hypothesized that cats with advanced heart disease including congestive heart failure from a variety of causes will tolerate pimobendan with a minimum of side effects when used in treatment in conjunction with a variety of other medications.Animals, materials and methodsOne hundred and seventy client owned cats with naturally occurring heart disease, one hundred and sixty four of which had congestive heart failure. Medical records were reviewed and owners and referring veterinarians were contacted for follow-up data. Data collected included pimobendan dose, other medications administered concurrently, data collected at physical examination, presence or absence of heart failure, adverse effects, classification of heart disease, echocardiographic data and survival time. The data were analyzed for significance between the initial visit and any follow-up visits.ResultsAll cats were treated with pimobendan. The median pimobendan dose was 0.24 mg/kg q 12 h. Pimobendan was used in combination with multiple concurrent medications including angiotensin converting enzyme inhibitors, diuretics and anti-thrombotics. Five cats (3.0%) had potential side effects associated with pimobendan. One cat (0.6%) had presumed side effects severe enough to discontinue pimobendan use. Median survival time for 164 cats with congestive heart failure after initiation of pimobendan was 151 days (range 1–870).ConclusionPimobendan appears to be well tolerated in cats with advanced heart disease when used with a variety of concurrent medications. Randomized controlled studies need to be performed to accurately assess whether it is efficacious for treatment of congestive heart failure in cats.  相似文献   

9.
Pimobendan is an inodilator used in the treatment of canine congestive heart failure (CHF). The aim of this study was to investigate the pharmacokinetics and cardiovascular effects of a nonaqueous oral solution of pimobendan using a single‐dose, operator‐blinded, parallel‐dose study design. Eight healthy dogs were divided into two treatment groups consisting of water (negative control) and pimobendan solution. Plasma samples and noninvasive measures of cardiovascular function were obtained over a 24‐h period following dosing. Pimobendan and its active metabolite were quantified using an ultra‐high‐performance liquid chromatography–mass spectrometer (UHPLC‐MS) assay. The oral pimobendan solution was rapidly absorbed [time taken to reach maximum concentration (Tmax) 1.1 h] and readily converted to the active metabolite (metabolite Tmax 1.3 h). The elimination half‐life was short for both pimobendan and its active metabolite (0.9 and 1.6 h, respectively). Maximal cardiovascular effects occurred at 2–4 h after a single oral dose, with measurable effects occurring primarily in echocardiographic indices of systolic function. Significant effects persisted for <8 h. The pimobendan nonaqueous oral solution was well tolerated by study dogs.  相似文献   

10.
OBJECTIVES: To evaluate the clinical efficacy and safety of pimobendan by comparing it with ramipril over a six-month period in dogs with mild to moderate heart failure (HF) caused by myxomatous mitral valve disease (MMVD). METHODS: This was a prospective randomised, single-blind, parallel-group trial. Client-owned dogs (n = 43) with mild to moderate HF caused by MMVD were randomly assigned to one of two groups, which received either pimobendan (P dogs) or ramipril (R dogs) for six months. The outcome measures studied were: adverse HF outcome, defined as failure to complete the trial as a direct consequence of HF; maximum furosemide dose (mg/kg/day) administered during the study period; and any requirement for additional visits to the clinic as a direct consequence of HF. RESULTS: Treatment with pimobendan was well tolerated compared with treatment with ramipril. P dogs were 25 per cent as likely as R dogs to have an adverse HF outcome (odds ratio 4.09, 95 per cent confidence interval 1.03 to 16.3, P = 0.046). CLINICAL SIGNIFICANCE: R dogs had a higher overall score and thus may have had more advanced disease than P dogs at baseline (P = 0.04). These results should be interpreted cautiously but such a high odds ratio warrants further investigation.  相似文献   

11.
Seventy-six dogs with clinical acquired atrioventricular valvular disease were evaluated to determine the efficacy of pimobendan (n=41) versus benazepril hydrochloride (n=35) in a randomized, positive-controlled, multicenter study. The study was divided into 56-day and long-term evaluation periods. In a subgroup of dogs with concurrent furosemide treatment (pimobendan [n=31], benazepril [n=25]), the Heart Insufficiency Score improved in favor of pimobendan (P=0.0011), equating to a superior overall efficacy rating (P<0.0001) at day 56. Long-term median survival (i.e., death or treatment failure) for dogs receiving pimobendan was 415 days versus 128 days for dogs not on pimobendan (P=0.0022).  相似文献   

12.
Background: Tissue Doppler imaging (TDI) including strain and strain rate (SR) assess systolic and diastolic myocardial function.
Hypothesis: TDI, strain, and SR variables of the left ventricle (LV) and the interventricular septum (IVS) differ significantly between dogs with myxomatous mitral valve disease (MMVD) with and without congestive heart failure (CHF).
Animals: Sixty-one dogs with MMVD with and without CHF. Ten healthy control dogs.
Methods: Prospective observational study.
Results: Radial motion : None of the systolic variables were altered and 3 of the diastolic velocities were significantly increased in dogs with CHF compared with dogs without CHF and control dogs. Longitudinal motion : 2 systolic velocities and 3 diastolic velocities were significantly increased in dogs with CHF compared with dogs without CHF and control dogs. Difference in systolic velocity time-to-peak between LV and IVS was significantly increased in dogs with MMVD with and without CHF compared with control dogs. In total, 11 (23%) of 48 TDI and strain variables differed significantly between groups. Left atrial to aortic ratio was positively correlated to early diastolic velocities, percentage increase in left ventricular internal diameter in systole was positively correlated to systolic and diastolic velocities, and mitral E wave to peak early diastolic velocity in the LV basal segment (E/Em) was positively correlated to radial strain and SR.
Conclusions and Clinical Importance: Few TDI and strain variables were changed in dogs with MMVD with and without CHF. Intraventricular dyssynchrony may be an early sign of MMVD or may be an age-related finding.  相似文献   

13.
Pimobendan has a dual mechanism of action: it increases myocardial contractility by increasing calcium sensitization to troponin C and it promotes vasodilation by inhibiting PDEIII. This study examined the effects of pimobendan on cardiac function, hemodynamics, and neurohormonal factors in dogs with mild mitral regurgitation (MR). The dogs were given 0.25 mg/kg of pimobendan orally every 12 hr for 4 weeks. With pimobendan, the heart rate and stroke volume did not change, but the systolic blood pressure gradually decreased and the degree of mitral valve regurgitation tended to decrease. Renal blood flow was significantly increased and the glomerular filtration rate was slightly increased at 2 and 4 weeks. Furthermore, over the 4-week period, the plasma norepinephrine concentration decreased significantly, the systolic index increased slightly, the left atrial diameter and the left ventricular diameters decreased significantly, and the heart size improved. Given these results, pimobendan appears to be useful for treating MR in dogs. However, further long-term studies of pimobendan involving a larger number of dogs with mild and moderate MR are needed to establish the safety of pimobendan and document improvements in quality of life.  相似文献   

14.
Plasma N-terminal pro-atrial natriuretic peptide (NT-proANP) concentration increases with progression of myxomatous mitral valve disease (MMVD) in dogs. This multicentre, prospective study compared plasma NT-proANP, N-terminal pro-brain natriuretic peptide (NT-proBNP), ANP, and cardiac troponin I (cTnI) concentrations in dogs with MMVD for their characteristics and discriminatory ability to detect cardiac dilatation and congestive heart failure (CHF). Thirty-six healthy dogs and 69 dogs with MMVD were included. Clinical variables were obtained via physical examination, thoracic radiography, and echocardiography. The discriminatory ability of each cardiac biomarker (CB) to determine the presence or absence of cardiac dilatation (event 1) and CHF (event 2) was evaluated using the receiver operating characteristic curves. Plasma NT-proANP, NT-proBNP, and ANP concentrations showed a significant association with the left atrium/aorta ratio (P<0.01). The area under the curve of plasma NT-proANP and NT-proBNP concentrations were 0.72 and 0.75, respectively in event1 and 0.72 and 0.76, respectively in event2. Plasma NT-proANP and NT-proBNP concentrations showed sensitivity 80.0 and 80.0%; specificity 67.6 and 64.7% in event1 (cutoff value; 8,497.81 pg/ml and 1,453.00 pmol/l, respectively) and sensitivity 85.7 and 81.0%; specificity 60.4 and 64.6% in event2 (cutoff value; 8,684.33 pg/ml and 1,772.00 pmol/l, respectively). In dogs with MMVD, plasma NT-proANP, NT-proBNP, and ANP concentrations increase with left atrial enlargement. Particularly, plasma NT-proANP and NT-proBNP concentrations appeared to be equally useful in the discriminatory ability to detect cardiac dilatation and CHF.  相似文献   

15.

Background

Cough often is reported as the primary clinical sign of congestive heart failure (CHF) in dogs with chronic degenerative myxomatous mitral valve disease (MMVD). Concurrent airway disease and compression of the left mainstem bronchus by a large left atrium also have been proposed as potential causes of coughing in these patients.

Objectives

To investigate the association between the presence of coughing and different potential causes of cough, including CHF, abnormal radiographic airway pattern, and cardiomegaly in dogs affected by naturally acquired MMVD.

Animals

Two hundred six client‐owned dogs.

Methods

Retrospective analysis performed on medical records of dogs affected by MMVD that underwent full cardiac evaluation, including echocardiographic examination and thoracic radiography.

Results

Univariate analyses showed that CHF is not a predictor of coughing (OR = 1.369; 0.723, 2.594), whereas abnormal radiographic airway pattern (OR = 3.650; 2.051, 6.496) and increased left atrial size observed radiographically (OR = 3.637; 1.904, 6.950) or echocardiographically (OR = 2.553; 1.436, 4.539) were significantly associated with coughing in dogs with MMVD. The same risk factors were significant in multivariate analyses.

Conclusions and Clinical Importance

This study indicates that CHF is not significantly associated with coughing in dogs with MMVD. Instead, abnormal radiographic airway pattern and left atrial enlargement are associated with coughing in these patients. This important finding should be taken into account when considering diagnosis and clinical management of CHF in these dogs.  相似文献   

16.
To support their combined use, the objective of the study was to evaluate the effects of benazepril and pimobendan on serum angiotensin‐converting enzyme (ACE) activity in dogs. A total of 48 healthy beagle dogs were randomized into four groups (n = 12 per group) in a parallel‐group design study: A (control, placebo twice daily (BID)); B (0.5–1.0 mg/kg benazepril once daily (SID) in the morning, placebo in the evening); C (0.25–0.5 mg/kg benazepril BID); D (0.25–0.5 mg/kg benazepril and 0.125–0.25 mg/kg pimobendan, both BID). The test items were administered orally for 15 days. Serum ACE activity was measured on days 1 and 15. Groups B, C and D had significantly lower average serum ACE activity compared to baseline and to the control group, on both days 1 and 15. There were no significant differences in average ACE activity between groups B, C and D. Noninferiority of group C to B was demonstrated. In conclusion, 0.25–0.5 mg/kg benazepril administered BID produced noninferior inhibition of serum ACE activity compared to 0.5–1.0 mg/kg benazepril dosed SID. Pimobendan had no significant effect on benazepril's action on serum ACE activity. The results support the use of benazepril BID in dogs and in combination with pimobendan.  相似文献   

17.
OBJECTIVE: To determine the efficacy of long-term enalapril administration in delaying the onset of congestive heart failure (CHF). DESIGN: Placebo-controlled, double-blind, multicenter, randomized trial. ANIMALS: 124 dogs with compensated mitral valve regurgitation (MR). PROCEDURES: Dogs randomly assigned to receive enalapril or placebo were monitored for the primary endpoint of onset of CHF for < or = 58 months. Secondary endpoints included time from study entry to the combined endpoint of CHF-all-cause death; number of dogs free of CHF at 500, 1,000, and 1,500 days; and mean number of CHF-free days. RESULTS: Kaplan-Meier estimates of the effect of enalapril on the primary endpoint did not reveal a significant treatment benefit. Chronic enalapril administration did have a significant benefit on the combined endpoint of CHF-all-cause death (benefit was 317 days [10.6 months]). Dogs receiving enalapril remained free of CHF for a significantly longer time than those receiving placebo and were significantly more likely to be free of CHF at day 500 and at study end. CONCLUSIONS AND CLINICAL RELEVANCE: Chronic enalapril treatment of dogs with naturally occurring, moderate to severe MR significantly delayed onset of CHF, compared with placebo, on the basis of number of CHF-free days, number of dogs free of CHF at days 500 and study end, and increased time to a combined secondary endpoint of CHF-all-cause death. Improvement in the primary endpoint, CHF-free survival, was not significant. Results suggest that enalapril modestly delays the onset of CHF in dogs with moderate to severe MR.  相似文献   

18.
Cytokines have been associated with the progression of congestive heart failure (CHF) in humans and may be implicated in the pathophysiology of myxomatous mitral valve disease (MMVD) in dogs. The aim of this study was to determine the serum concentrations of cytokines in dogs with MMVD. The study included 16 Cairn terriers with no or minimal mitral regurgitation (MR), 41 Cavalier King Charles Spaniels (CKCS) with different degrees of MR and 11 dogs of different breeds with CHF due to MMVD. Granulocyte-macrophage colony-stimulating factor, interferon-γ, interleukin (IL)-2, IL-6, IL-7, IL-8, IL-10, IL-15, IL-18, keratinocyte-derived chemokine, interferon-γ-induced protein and monocyte chemoattractant protein-1 (MCP-1) were measured using a canine-specific multiplex immunoassay. CHF dogs had significantly higher MCP-1 concentrations than dogs with no or minimal MR. Among the CKCS, IL-2 and IL-7 decreased with increasing left atrial size and IL-7 also decreased with increasing MR. IL-8 decreased with increasing left ventricular end-systolic internal dimensions. MCP-1 was increased in CHF dogs compared to healthy control dogs and IL-2, IL-7 and IL-8 decreased with increasing indices of disease severity. The results suggest a role for these cytokines in canine MMVD and CHF.  相似文献   

19.
Background: The renin-angiotensin-aldosterone system (RAAS) is activated in states of decreased cardiac output and by certain cardiovascular therapeutic agents, such as loop diuretics and vasodilators.
Hypothesis: Short-term treatment with the inodilator, pimobendan, will not activate the circulating RAAS because its vasodilatory action will be offset by its positive inotropic property, thereby ameliorating RAAS stimulation at the juxtaglomerular apparatus. Furthermore, pimobendan will suppress RAAS activation produced by furosemide.
Animals: Nine healthy laboratory dogs were used in this study.
Methods: Experimental, cross-over study. Dogs were administered pimobendan (0.5 mg/kg q12h) for 4 days followed by furosemide (2 mg/kg q12h) and then, after a wash-out period, a combination of the drugs. Aldosterone : creatinine (A : Cr) was measured at the end of each treatment cycle.
Results: There was no significant increase in the average urinary A : Cr with the administration of pimobendan (control urinary A : Cr = 0.46, standard deviation (SD) 0.33; pimobendan A : Cr = 0.48, SD 0.28). There was a significant increase in the average urinary A : Cr after administration of furosemide (urinary A : Cr = 1.3, SD 0.70) and with the combination of furosemide and pimobendan (urinary A : Cr = 2.9, SD 1.6).
Conclusions and Clinical Relevance: Short-term administration of high-dose pimobendan, does not activate the RAAS in healthy dogs. Pimobendan did not prevent RAAS activation associated with furosemide therapy. These results in healthy dogs suggest that furosemide therapy, with or without pimobendan, should be accompanied by RAAS suppressive therapy.  相似文献   

20.
Pimobendan is a benzimidazole‐pyridazinone derivative, marketed as a racemic mixture for the management of canine heart failure. Pharmacokinetics of the enantiomers of pimobendan and its oral bioavailability have not been described in dogs. The aim of this study was to describe pharmacokinetics of three formulations of pimobendan in healthy dogs: the licensed capsule product, and novel liquid and intravenous formulations. A three‐period, nested randomized two‐treatment crossover design was used. Pimobendan was administered p.o. at 0.25 and i.v. at 0.125 mg/kg. Blood and plasma samples were analysed by liquid chromatography–mass spectrometry. Noncompartmental modelling was used to describe the pharmacokinetics. Parameters were compared between formulations using a general linear model. Bioequivalence of the oral formulations was tested using CI90 for AUC(0–∞) and Cmax. Bioavailability of pimobendan after oral dosing was 70%. Liquid and capsule formulations were bioequivalent only for AUC. The positive enantiomer of pimobendan (PE) had a larger volume of distribution than the negative enantiomer (NE) (281 ± 48 vs. 215 ± 68 mL/kg; P = 0.003) and a shorter half‐life (21.7 vs. 29.9 min; P = 0.004). The NE was distributed more quickly than the PE into blood cells. Enantiomers of pimobendan have differing absorption, distribution and elimination. The pharmacokinetics of pimobendan in healthy dogs was described.  相似文献   

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