Comparison of plasma cocaine levels during a "binge" pattern of cocaine administration in male and female rhesus monkeys

Abstract

Rationale. Cocaine is often abused in a "binge" pattern, but little is known about changes in plasma cocaine concentrations or cocaine pharmacokinetics during administration of multiple cocaine doses. Moreover, the extent to which gender may influence plasma cocaine levels during a cocaine binge has not been studied in rhesus monkeys.

Objectives. To compare the effects of repeated injections of the same dose of cocaine (0.4 mg/kg or 0.8 mg/kg, i.v.) on plasma cocaine concentrations, cocaine pharmacokinetics and behavioral responses in male and female rhesus monkeys.

Methods. Four injections of cocaine (0.4 mg/kg or 0.8 mg/kg, i.v.) were administered at 30-min intervals to five or six male and five or six female rhesus monkeys. Samples for plasma cocaine analysis were collected at 2, 4, 8, 16 and 24 min after the first three injections. After the fourth cocaine injection, additional samples were collected at 10-min intervals over 150 min.

Results. Plasma cocaine peaks and nadirs increased monotonically after successive cocaine injections (P<0.0001). Peak plasma cocaine levels measured at 2 min after cocaine administration were higher after 0.8 mg/kg cocaine than after 0.4 mg/kg cocaine (P<0.006). There were no significant gender differences in time to peak plasma cocaine levels (t_max), peak cocaine concentrations (C_max) or half-life (t_1/2; min) at either dose of cocaine. Group average behavioral ratings were similar in males and females after each dose of cocaine.

Conclusions. Peak plasma cocaine concentrations increased progressively during low and high dose cocaine binge episodes, and there were no significant gender differences in cocaine pharmacokinetics. These findings demonstrate the feasibility of simulating "binge" patterns of cocaine administration in rhesus monkeys.