Pharmacokinetics Of Alpha-Pyrrolidinovalerophenone In Male Rats With And Without Vaccination With An Alpha-Pyrrolidinovalerophenone Vaccine

PURPOSE: alpha-Pyrrolidinovalerophenone (alpha-PVP) is a second-generation synthetic cathinone which acts as an inhibitor at the dopamine and norepinephrine transporters in the brain. These novel studies determined the pharmacokinetics (PK) of alpha-PVP in rats and then evaluated the effects of an alpha-PVP vaccine on the PK profile. METHODS: Adult male Sprague-Dawley rats were randomly divided into treatment groups (n = 24/group) in which the vaccinated rats received an initial and two booster immunizations of the alpha-PVP vaccine at 0, 3, and 9 wks. Control rats received saline injections. alpha-PVP (0.56, 1, 3 mg/kg, sc) was then administered to both groups between 11-12 weeks and serum samples were collected for determination of alpha-PVP serum concentrations by LC-MS/MS (n=6 rats/treatment/time). At 13 weeks, brain, heart and kidney concentrations of alpha-PVP were determined by LC-MS/MS after administration of 1 mg/kg alpha-PVP (n=4-5 rats/treatment/time). RESULTS: PK values in control rats showed dose-dependent increases in maximum serum concentrations (C-max) and area under the curve (AUC(inf)) values with an elimination half-life (t(1/2)) of approximately 2.1 h. alpha-PVP exhibited linear PK profile in control rats. Vaccinated rats had significantly (p<0.05) higher serum C-max and AUC(inf) values than controls, and significantly reduced total body clearance, volume of distribution and t1/2 values. Vaccinated rats had significantly lower alpha-PVP concentrations in the brain, heart, and kidney in comparison to control rats at early time points. CONCLUSION: Vaccination with the novel alpha-PVP vaccine significantly altered serum PK leading to a time-dependent reduction in brain, kidney and heart concentrations of alpha-PVP compared to controls.