Pharmacokinetics of (+)-methamphetamine (METH) and its metabolite (+)-amphetamine (AMP) in a METH self-administration paradigm in rats

Background Most pre-clinical and clinical studies characterize the pharmacokinetics (PK) of METH using single-dose designs. To better understand METH effects in a more clinically relevant model, we studied the PK of METH and AMP in a self-administration paradigm. Methods Dual cannulated male rats (n=5) were given METH via an infusion pump. The pump was programmed to deliver multiple METH injections of 0.048 mg/kg based on actual METH self-administration patterns in rats. Blood samples were collected at multiple time points and METH and AMP concentrations were determined by LC/MS/MS. Results Relatively stable METH concentrations were achieved within the first 30 min. of METH dosing. PK analysis showed that half-life, volume of distribution, total clearance and amount of AMP formed were not statistically different from values found after a single METH dose. Conclusion These data showed rats self-administered loading doses of METH, which resulted in rapidly reaching steady-state concentrations. This multiple dosing model should prove useful in understanding the interplay between METH PK and self-administration behavior. Clinical Pharmacology & Therapeutics (2005) 77, P81–P81; doi: 10.1016/j.clpt.2004.12.200