Pharmacologic interactions between transdermal selegiline and cocaine

Selegiline may be efficacious in treatment of cocaine addiction. This study assessed pharmacokinetic (PK) and pharmacodynamic (PD) interactions between transdermal (TD) selegiline and cocaine in 14 nondependent, cocaine-experienced volunteers challenged with IV cocaine-d₅ before and after TD selegiline. To obtain steady state conditions for cocaine rapidly, a 0.5 mg/kg loading dose (over 10 min) was followed by a 4 hr infusion of 2.0 mg/kg. Transdermal selegiline was administered as one 20 mg/patch/day (Somerset Pharmaceuticals) applied after the first cocaine infusion and continued for 10 days. The second cocaine challenge was performed following 1 days of selegiline, at selegiline steady-state (determined by urine PK analysis). PD effects of cocaine (heart rate, blood pressure, respiratory rate, skin and tympanic temperature) were not altered by selegiline. Adverse reactions to TD selegiline were minimal with no orthostatic vital sign changes and no adverse cardiovascular reactions. Selegiline and its levo-metabolites had all reached steady-state after approximately 5 days. Plasma cocaine PK was unaffected by selegiline administration. These results suggest that TD selegiline is safe and may be useful in the treatment of cocaine dependence.