Pimobendan

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Pimobendan
Systematic (IUPAC) name
(RS)-6-[2-(4-methoxyphenyl)-1H-benzimidazol-5-yl]-5-methyl-4,5-dihydropyridazin-3(2H)-one
Clinical data
AHFS/Drugs.comInternational Drug Names
Pregnancy cat. ?
Legal status Prescription only
RoutesOral
Pharmacokinetic data
Bioavailability60 to 65%
Half-life0.4 hours
ExcretionIn feces
Identifiers
CAS number74150-27-9 YesY
ATCvet codeQC01CE90
PubChemCID 4823
UNII34AP3BBP9T N
KEGGD01133 YesY
ChEMBLCHEMBL24646 N
Chemical data
FormulaC19H18N4O2 
Mol. mass334.37 g/mol
 N (what is this?)  (verify)
 
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Pimobendan
Systematic (IUPAC) name
(RS)-6-[2-(4-methoxyphenyl)-1H-benzimidazol-5-yl]-5-methyl-4,5-dihydropyridazin-3(2H)-one
Clinical data
AHFS/Drugs.comInternational Drug Names
Pregnancy cat. ?
Legal status Prescription only
RoutesOral
Pharmacokinetic data
Bioavailability60 to 65%
Half-life0.4 hours
ExcretionIn feces
Identifiers
CAS number74150-27-9 YesY
ATCvet codeQC01CE90
PubChemCID 4823
UNII34AP3BBP9T N
KEGGD01133 YesY
ChEMBLCHEMBL24646 N
Chemical data
FormulaC19H18N4O2 
Mol. mass334.37 g/mol
 N (what is this?)  (verify)

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.[1] 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.[2] Under the trade name Acardi, it is available for human use in Japan.[3]

Contents

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:

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:[4]

Pimobendan.png

See also

References

  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. http://www.jaaha.org/cgi/pmidlookup?view=long&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. doi:10.1111/j.1939-1676.2008.0150.x. PMID 18638016. 
  3. ^ "Kusuri-no-Shiori Drug Information Sheet". RAD-AR Council, Japan. April 2005. http://www.rad-ar.or.jp/siori/english/kekka.cgi?n=54. Retrieved 2008-08-06. 
  4. ^ Nicolas, C; Verny, M; Maurizis, J. C.; Payard, M.; Faurie, M (1986). "Synthesis of14C-bucromarone succinate and hydrochloride". J. Labeled Cmpd. Radiopharm. 23: 837. doi:10.1002/jlcr.2580230806. 

Further reading

External links