Pimobendan

Drugbox
IUPAC_name = 6- [2-(4-methoxyphenyl)-1"H"-benzimidazol-5-yl] -5-methyl-4,5-dihydropyridazin-3(2"H")-one

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CAS_number = 74150-27-9
CAS_supplemental =
ATC_prefix =
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ATC_supplemental =
PubChem = 4823
DrugBank =
chemical_formula =
C=19 | H=18 | N=4 | O=2
molecular_weight = 334.37 g/mol
smiles = CC1CC(=O)NN=C1C2=CC3=C(C=C2)N=C(N3)C4=CC=C(C=C4)OC
bioavailability = 60 to 65%
protein_bound =
metabolism =
elimination_half-life = 0.4 hours
excretion = In feces
pregnancy_AU =
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legal_status = Rx-only
routes_of_administration = Oral

Pimobendan (INN, manufactured by Boehringer Ingelheim under the trade names Vetmedin and Acardi), also known as pimobendane, is a calcium sensitizer with positive inotropic and vasodilator effects. It is also a selective inhibitor of phosphodiesterase III (PDE3).

Pimobendan is used in the management of heart failure in dogs, most commonly caused by myxomatous mitral valve disease (also known as endocardiosis), or dilated cardiomyopathy. [cite journal |author=Gordon SG, Miller MW, Saunders AB |title=Pimobendan in heart failure therapy—a silver bullet? |journal=J Am Anim Hosp Assoc |volume=42 |issue=2 |pages=90–3 |year=2006 |pmid=16527909 |doi= |url=http://www.jaaha.org/cgi/pmidlookup?view=long&pmid=16527909] Research has shown that pimobendan increases survival time and improves quality of life in patients with congestive heart failure when compared with benazepril, an angiotensin-converting-enzyme (ACE) inhibitor. [cite journal |author=Häggström J, Boswood A, O'Grady M, "et al" |title=Effect of Pimobendan or Benazepril Hydrochloride on Survival Times in Dogs with Congestive Heart Failure Caused by Naturally Occurring Myxomatous Mitral Valve Disease: The QUEST Study |journal=J. Vet. Intern. Med. |volume= |issue= |pages= |year=2008 |month=July |pmid=18638016 |doi=10.1111/j.1939-1676.2008.0150.x |url=] It is also available for human use in Japan, under the trade name Acardi. [cite web |url=http://www.rad-ar.or.jp/siori/english/kekka.cgi?n=54 |title=Kusuri-no-Shiori Drug Information Sheet |date=April 2005 |publisher=RAD-AR Council, Japan |accessdate=2008-08-06]

Mechanism of action

Pimobendan is a positive inotrope. It sensitizes and increase the binding efficency of cardiac myofibril to the calcium ions that are already present without increasing the consumption of oxygen and energy.Pimobendan also causes peripheral vasodilation by inhibiting the function of phosphodiesterase III. This results in decreased pressure, translating into smaller cardiac preload and afterload (decreases the failing heart's workload).

Pharmacokinetics

Pimobendan is absorbed rapidly when given via the oral route and has a bioavailability of 60-65%. It is metabolized into its active form by the liver. The half-life of pimobendan in the blood is 0.4 hours and the half-life of its metabolite is 2 hours. Elimination is by excretion in the bile and then, faeces. Pimobendan is 90–95% bound to plasma proteins in circulation. This has implications in patients suffering from low blood protein levels (hypoproteinemia/hypoalbuminemia) and with patients that are on concurrent therapies that are also highly protein bound.

Combinations

Pimobendan is often used in combination with three other drugs to palliate dogs with heart disease and reduce clinical signs of disease. These are:
*Furosemide, a diuretic, to reduce pulmonary oedema. This can be given intravenously if the animal is in respiratory distress (6-8mg/kg), and then titrated down to the minimum dose required orally.
*Spironolactone, an aldosterone antagonist. This has two actions, firstly, as a potassium-sparing diuretic, although its diuretic properties are small compared with those of furosemide. Secondly, it reduces aldosterone-mediated myocardial remodelling and fibrosis, slowing the progression of heart disease.
*An ACE inhibitor, often enalapril (trade name Enacard) or benazepril (Fortekor). These drugs inhibit the action of angiotensin-converting enzyme, producing a balanced vasodilation, along with other favourable effects.

Other drugs may also be used as required to manage certain arrhythmias that are often associated with heart disease.

ee also

*Levosimendan

References

Further reading

*cite journal |author=Lee JA, Allen DG |title=Calcium sensitisers |journal=BMJ |volume=300 |issue=6724 |pages=551–2 |year=1990 |month=March |pmid=2108746 |pmc=1662365

External links

*Vetmedin website ( [http://www.vetmedin.co.uk UK] and [http://www.vetmedin.com.au Australia] )
*Website about the QUEST study (reference 2) (http://www.questtrial.com)