Pimobendane

Pimobendan

File:Pimobendan skeletal.svg
Clinical data
AHFS/Drugs.com	International Drug Names
Routes of administration	Oral
ATCvet code	Template:Infobox drug/formatATCvet Template:Infobox drug/formatATCvet
Legal status
Legal status	In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability	60 to 65%
Elimination half-life	0.4 hours
Excretion	In feces
Identifiers
IUPAC name (RS)-6-[2-(4-methoxyphenyl)-1H-benzimidazol-5-yl]-5-methyl-4,5-dihydropyridazin-3(2H)-one
CAS Number	74150-27-9 Y
PubChem CID	4823
UNII	34AP3BBP9T
KEGG	D01133 Y
ChEMBL	ChEMBL24646 N
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}
Chemical and physical data
Formula	C19H18N4O2
Molar mass	334.37 g/mol
3D model (JSmol)	Interactive image
SMILES CC1CC(=O)NN=C1C2=CC3=C(C=C2)N=C(N3)C4=CC=C(C=C4)OC
NY (what is this?)  (verify)

_NOTOC_ Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Pimobendan (INN is a veterinary medication manufactured by Boehringer Ingelheim under the trade names Vetmedin and Acardi) or pimobendane. It 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. Research has shown that pimobendan increases survival time and improves quality of life in patients with congestive heart failure secondary to mitral valve disease when compared with benazepril, an angiotensin-converting-enzyme (ACE) inhibitor. Under the trade name Acardi, it is available for human use in Japan.

Mechanism of action

Pimobendan is a positive inotrope. It sensitizes and increases the binding efficiency 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 feces. 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 edema. This can be given intravenously if the animal is in respiratory distress (6–8 mg/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.

Chemistry

Pimobendan can be synthesized beginning with anisoyl chloride: