Clomipramine Hydrochloride Tablets belong to the dibenzazepine class of tricyclic antidepressants. Clomipramine hydrochloride is 3-chloro-5[3-(dimethyl-amino)propyl]-10,11 dihydro-5H dibenz[b,f]azepine monohydrochloride. Clomipramine Hydrochloride Tablets are oblong, light brown in color and contain clomipramine hydrochloride formulated together with meat components. The molecular weight of clomipramine hydrochloride is 351.3. The structural formula is:
Clomipramine hydrochloride reduces the clinical signs of separation anxiety by affecting serotonergic and noradrenergic neuronal transmission in the central nervous system. While clomipramine hydrochloride can cause lethargy in dogs (see Adverse Reactions) its mode of action is not as a sedative. Clomipramine hydrochloride's capacity to inhibit re-uptake of serotonin in the central nervous system is believed to be the primary mechanism of action. Clomipramine hydrochloride is rapidly absorbed when administered orally. A single-dose crossover study involving 12 dogs evaluated clomipramine hydrochloride bioavailability after IV (2 mg/kg) and oral (4 mg/kg) administration in either a fed or fasted state. The administration of clomipramine hydrochloride in the presence of food resulted in an increase in the rate and extent of drug absorption as shown in the following table (mean ±SD):
The absolute bioavailability is approximately 25% greater in fed dogs. The apparent terminal plasma half-life ranges from approximately 2 to 9 hours in fed and 3 to 21 hours in fasted dogs. The difference and variability in apparent half-life estimates may be attributable to prolonged drug absorption in the fasted state. The relatively large volume of distribution (3.8 ±0.8 L/kg) suggests that the drug is widely distributed throughout the body. Clomipramine is primarily metabolized in the liver.