Pimobendan

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Pimobendan
Pimobendan skeletal.svg
Systematic (IUPAC) name
(RS)-6-[2-(4-methoxyphenyl)-1H-benzimidazol-5-yl]-5-methyl-4,5-dihydropyridazin-3(2H)-one
Clinical data
AHFS/Drugs.com International Drug Names
Legal status
  • Prescription only
Routes Oral
Pharmacokinetic data
Bioavailability 60 to 65%
Half-life 0.4 hours
Excretion In feces
Identifiers
CAS number 74150-27-9 YesY
ATCvet code QC01CE90
PubChem CID 4823
ChemSpider 4657 N
UNII 34AP3BBP9T N
KEGG D01133 YesY
ChEMBL CHEMBL24646 N
Chemical data
Formula C19H18N4O2 
Mol. mass 334.37 g/mol
 N (what is this?)  (verify)

Pimobendan (or pimobendane)(INN) is a veterinary medication manufactured by Boehringer Ingelheim under the trade names Vetmedin and Acardi (Japan). It is both a calcium sensitizer and a selective inhibitor of phosphodiesterase III (PDE3) with positive inotropic and vasodilator effects.

Pimobendan is used in the management of heart failure in dogs, most commonly caused by myxomatous mitral valve disease (also previously known as endocardiosis), or dilated cardiomyopathy.[1] Research has shown that pimobendan increases survival time and improves quality of life in canine patients with congestive heart failure secondary to mitral valve disease when compared with benazepril, an angiotensin-converting-enzyme (ACE) inhibitor.[2] Under the trade name Acardi, it is available for human use in Japan.[3]

Mechanism of action[edit]

Pimobendan is a positive inotrope (increases myocardial contractility). It sensitizes and increases the binding efficiency of cardiac troponin in the myofibril to the calcium ions that are already present in systole. In normal hearts it increases the consumption of oxygen and energy to the same degree as dobutamine but in diseased hearts it may not.[4] [5] Pimobendan also causes peripheral vasodilation by inhibiting the function of phosphodiesterase III. This results in decreased resistance to blood flow through systemic arterioles, which decreases afterload (decreases the failing heart's workload) and reduces the amount of mitral regurgitation.[6][7]

Pharmacokinetics[edit]

Pimobendan is absorbed rapidly when given via the oral route and has a bioavailability of 60-65%.[8] Bioavailability is markedly decreased when ingested with food. It is metabolized into an active metabolite (desmethylpimobendan) by the liver. The parent compound, pimobendan, is a potent calcium sensitizer while desmethylpimobendan is a more potent phosphodiesterase III inhibitor.[9] 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 may have implications in patients suffering from low blood protein levels (hypoproteinemia/hypoalbuminemia) and in patients that are on concurrent therapies that are also highly protein bound.

Combinations[edit]

Pimobendan is often used in combination with three other drugs to palliate dogs with heart failure (pulmonary edema, pleural effusion, ascites). These are:

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

Synthesis[edit]

Pimobendan can be synthesized beginning with anisoyl chloride.

Pimobendan synthesis:[10]

See also[edit]

References[edit]

  1. ^ Gordon SG, Miller MW, Saunders AB (2006). "Pimobendan in heart failure therapy—a silver bullet?". J Am Anim Hosp Assoc 42 (2): 90–3. PMID 16527909. 
  2. ^ Häggström J, Boswood A, O'Grady M, et al. (July 2008). "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". J. Vet. Intern. Med. 22 (5): 1124–35. doi:10.1111/j.1939-1676.2008.0150.x. PMID 18638016. 
  3. ^ "Kusuri-no-Shiori Drug Information Sheet". RAD-AR Council, Japan. April 2005. Retrieved 2008-08-06. 
  4. ^ Hata K1, Goto Y, Futaki S, Ohgoshi Y, Yaku H, Kawaguchi O, Takasago T, Saeki A, Taylor TW, Nishioka T, et al. Mechanoenergetic effects of pimobendan in canine left ventricles. Comparison with dobutamine. Circulation. 1992 Oct;86(4):1291-301.
  5. ^ Goto Y1, Hata K. Mechanoenergetic effect of pimobendan in failing dog hearts. Heart Vessels. 1997;Suppl 12:103-5.
  6. ^ Verdouw PD, Hartog JM, Duncker DJ, Roth W, Saxena PR. Cardiovascular profile of pimobendan, a benzimidazole-pyridazinone derivative with vasodilating and inotropic properties. Eur J Pharmacol. 1986 Jul 15;126(1-2):21-30.
  7. ^ Kanno N, Kuse H, Kawasaki M, Hara A, Kano R, Sasaki Y. Effects of pimobendan for mitral valve regurgitation in dogs. J Vet Med Sci. 2007 Apr;69(4):373-7.
  8. ^ http://www.vetmedin.com/Vetmedin%20Insert_6-07.pdf
  9. ^ Hanzlicek AS1, Gehring R, Kukanich B, Kukanich KS, Borgarelli M, Smee N, Olson EE, Margiocco M. Pharmacokinetics of oral pimobendan in healthy cats. J Vet Cardiol. 2012 Dec;14(4):489-96.
  10. ^ Nicolas, C.; Verny, M.; Maurizis, J. C.; Payard, M.; Faurie, M. (1986). "Synthesis of 14C-bucromarone succinate and hydrochloride". Journal of Labelled Compounds and Radiopharmaceuticals 23 (8): 837. doi:10.1002/jlcr.2580230806.  edit

Further reading[edit]

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