Within-subject variability in cocaine pharmacokinetics and pharmacodynamics after intraperitoneal compared with...

Performance in rats (Rattus norvegicus) was measured on a differential reinforcement of low-rate schedule (DRL 45-s) in 1.5-hr sessions after 2 mg/kg intravenous (i.v.) or 10-20 mg/kg intraperitoneal (i.p.) cocaine administration, with each dose given twice and separated by 3-5 days. For successive i.v. doses, cocaine effects were similar, with minimal within-subject variability. For i.p. cocaine, the effects were not always similar; performance was variable and sometimes remained at baseline level. These diminished effects occurred following either the 1st or 2nd i.p. injection. A parallel pharmacokinetic study of cocaine confirmed that within-subject variability existed in cocaine concentration-time profiles after i.p. cocaine, and that a low serum cocaine concentration-time profile could account for the diminished effects. The i.p. route for cocaine administration should be used with caution.