PHARMACEUTICAL FORM
Oral solution.
Clear green solution.
PHARMACOLOGICAL PROPERTIES
Pharmacodynamic properties
The veterinary medicinal product contains tasipimidine as the active substance.
Tasipimidine is a potent and selective alpha-2A adrenoceptor agonist (as
demonstrated in human adrenoceptors) that inhibits the release of noradrenaline
from noradrenergic neurons, blocks the startle reflex and thus counteracts arousal.
Tasipimidine as an alpha-2 adrenoceptor agonist reduces the over activation of
noradrenergic neurotransmission (increased release of noradrenaline in the locus
coeruleus), which is shown to induce anxiety and fear in experimental animals
exposed to stressful situations.
In summary, tasipimidine exerts its effects by decreasing central noradrenergic
neurotransmission. In addition to the anxiolytic effect, tasipimidine can cause other
known dose dependent alpha-2 adrenoceptor-mediated pharmacological effects such
as sedation, analgesia and lowering of heart rate, blood pressure and rectal
temperature.
The onset of effect is usually seen within 1 hour after treatment administration. The
duration of effect shows some individual variation, and it can last for up to 3 hours or
longer.
Pharmacokinetic particulars
Absorption
After oral administration in solution, tasipimidine is rapidly absorbed in fasted dogs. In
a pharmacokinetic study in fasted dogs, a moderate oral bioavailability of tasipimidine
was observed being on average 60%. After oral administration of 30 μg/kg to dogs in
fasted state, the maximum plasma concentration of tasipimidine is approximately
5 ng/ml and occurs at 0.5–1.5 hours. When the dosing is repeated 3 hours later, the
following maximum plasma concentration is shown to be moderately (30%) higher
but there is no effect on the time of maximum concentration. Feeding at the time of
dosing slows down the absorption and decreases the maximum plasma levels. In fed
state the peak concentration is lower being 2.6 ng/ml and comes later at 0.7–6 hours.
The total plasma exposure to tasipimidine is comparable in fasted and fed states.
Systemic exposure increases approximately in a dose proportional manner within the
dose range of 10–100 μg/kg. No signs of accumulation are seen after repeated
administration.
Distribution
Tasipimidine is a highly distributed compound, the volume of distribution in dogs is
3 l/kg. Tasipimidine penetrates the brain tissue in dogs and the drug concentration
after repeated administration is higher in brain than in plasma. The in vitro binding of
tasipimidine to dog plasma proteins is low, approximately 17%.
Metabolism
The metabolism of tasipimidine occurs mainly through demethylation and
dehydrogenation and the most abundant circulating metabolites are demethylation
and dehydrogenation products. The demethylated dehydrogenation product of
tasipimidine is found in trace levels in dog plasma after high doses. The circulating
metabolites are much less potent than the parent drug, as demonstrated in human
and rat adrenoceptors.
ExcretionTasipimidine is a highly cleared compound being rapidly eliminated from the
circulation of dogs. The total clearance is 21 ml/min/kg after 10 μg/kg i.v. bolus dose.
The mean terminal half-life is 1.7 hours after oral administration in fasted state. The
portion of tasipimidine excreted unchanged in urine is 25%. All the circulating
metabolites are excreted in urine much less compared to tasipimidine.
PHARMACEUTICAL PARTICULARS
List of excipients
Sodium benzoate (E211)
Sodium citrate
Citric acid monohydrate
Brilliant blue (E133)
Tartrazine (E102)
Purified water
Major incompatibilities
In the absence of compatibility studies, this veterinary medicinal product must not be
mixed with other veterinary medicinal products.
Shelf life
Shelf life of the veterinary medicinal product as packaged for sale: 3 years.
Shelf life after first opening the immediate packaging: 12 months in a refrigerator
(2°C to 8°C) or 1 month below 25°C.
Special precautions for storage
Store in a refrigerator (2°C to 8°C). Keep the bottle in the outer carton in order to
protect from light.
Nature and composition of immediate packaging
15 ml clear glass type III bottle with a polypropylene child-resistant closure and a lowdensity
polyethylene adapter and a high-density polyethylene liner. An oral lowdensity
polyethylene/polystyrene syringe is included in the pack.
Pack sizes:
Cardboard box with 1 bottle and an oral syringe.
Special precautions for the disposal of unused veterinary medicinal
product or waste materials derived from the use of such products
Any unused veterinary medicinal product or waste materials derived from such
veterinary medicinal product should be disposed of in accordance with local
requirements.