Arteriovenous serum cocaine concentration difference after intravenous bolus injection and constant-rate infusions: relation to pharmacodynamic estimates in rats.

We characterized the pharmacokinetics of cocaine using both arterial and venous serum data after a bolus dose (2 mg/kg) and two constant-rate infusions (12.24 and 24.48 microg/min) for 2 h in rats. A published behavioral effect was used to investigate the effects of arteriovenous serum concentration differences on pharmacodynamic estimates for the 2 mg/kg dose. Significant temporal arteriovenous serum cocaine and benzoylecgonine (the major metabolite) concentration differences existed after cocaine administrations. The AUCs for arterial serum data were greater than the AUCs for venous data, indicating that cocaine was metabolized more extensively in the venous sampling site. Cocaine's behavioral effect could be directly related to serum concentrations with no hysteresis observed between the effects and arterial or venous serum concentrations. The pharmacodynamic estimates derived from arterial serum data approximated those from the venous data due to the most decline of cocaine's effect occurred in the elimination phase during which serum cocaine concentrations were not significantly different between the two sampling sites.