THE PHARMACOKINETICS AND ABSOLUTE BIOAVAILABILITY OF SELEGILINE IN THE DOG

Selegiline is beneficial to Parkinsonian patients as an adjunct to lev odopa therapy. Currently no pharmacokinetic data are available for sel egiline in the literature, mainly due to lack of analytical methods th at can measure concentrations below 10 ng mL(-1) in plasma. A sensitiv e fluorimetric assay based on inhibition of rat brain monoamine oxidas e-B (MAO-B) in vitro has been developed to measure selegiline in plasm a as low as 0.25 ng mL(-1). The pharmacokinetics of selegiline were in vestigated following intravenous and oral administration to four femal e mongrel dogs. Each dog received 1 mg kg(-1) selegiline in solution v ia gavage or by an intravenous route separated by one week. The mean t erminal half-life, volume of distribution of the central compartment, and systemic clearance of selegiline were 60.24+/-9.56 min, 6.56+/-0.5 6 L kg(-1), and 159.91+/-19.28 mL min(-1) kg(-1), respectively. After oral administration selegiline appeared to be absorbed rapidly with a t(max) and C-max of 25+/-5.8 min and 5.2+/-1.36 ng mL(-1), respectivel y. The absolute bioavailability of selegiline in the dog was 8.51+/-3. 31%.