Pharmacokinetics and bioavailability of selegiline in the dog using an enzymatic assay

The clinical features of Parkinsonism result from a depletion of dopamine transmission in the corpus striatum; the dopamine deficiency is caused by a loss of melanin-containing nerve cells within the substantia nigra. Though the mainstay of the therapy is levodopa, selegiline is beneficial to parkinsonian patients as an adjuvant to levodopa therapy. Selegiline acts by inhibiting Monoamine oxidase-B (MAO-B), thus elevating the dopamine concentration in the brain. Selegiline is also being evaluated in veterinary medicine for treatment of Cushing's syndrome and reduce the symptoms of cognitive dysfunction in the dog. A dose of 2 mg/kg orally to dogs has assisted in reducing memory loss. Currently no pharmacokinetics data is available for selegiline in the literature, mainly due to lack of analytical methods which can measure concentrations less than 10 ng/ml in plasma.;The pharmacokinetics of selegiline were investigated following intravenous and oral administration to four female mongrel dogs. Each dog received 1 mg/kg selegiline in solution via gavage or by intravenous administration in cross-over studies separated by one week. Plasma samples were analyzed by the enzymatic method. The mean terminal half-life, the volume of distribution of central compartment and systemic clearance of selegiline were 56.04 ;A sensitive fluorometric assay based on inhibition of rat brain Monoamine oxidase-B (MAO-B) in vitro has been described. The procedure measures the inhibition of MAO-B activity produced by the addition of selegiline extracted from plasma. Selegiline concentrations as low as 0.25 ng/ml can be detected. The standard curve was linear from 125 picogram (0.25 ng/ml) to 4000 picogram (8.0 ng/ml) in the incubation tube.