Pharmacodynamic properties
Pimobendan, a benzimidazole-pyridazinone derivative, is a non-sympathomimetic, non-glycoside inotropic substance with potent vasodilatative properties. Pimobendan exerts its stimulatory myocardial effect by a mechanism of action: increases in calcium sensitivity of cardiac myofilaments and inhibition of phosphodiesterase (type III). It also exhibits a vasodilatory action through an inhibitory action on phosphodiesterase III activity. The combined evidence from cell culture, laboratory animal and small studies in the target species suggests that the combination of the specific PD properties of pimobendan may reduce the progression of myocardial damage in dogs with MVD and DCM when used together with other standard therapy.
Pharmacokinetic particulars
Absorption Following oral administration of Vetmedin capsules the absolute bioavailability of the active principle is 60 – 63%. Since this bioavailability is considerably reduced when pimobendan is administered with food or shortly thereafter, it is recommended to treat animals approximately 1 hour before feeding.
Distribution The volume of distribution is 2.6 l/kg, indicating that pimobendan is distributed readily into the tissues. The mean plasma protein binding is 93%
Metabolism The compound is oxidatively demethylated to its major active metabolite (UD-CG 212). Further metabolic pathways are phase II conjugates of UD-CG-212, in essence glucuronides and sulphates.
Elimination The plasma elimination half-life of pimobendan is 0.4±0.1 hours which is consistent with a high clearance of 90±19 ml/min/kg and a short mean residence time of 0.5 ± 0.1hours.
The main active metabolite is eliminated with a plasma elimination half-life of 2.0 ± 0.3 hours. Almost the entire dose is eliminated via faeces.