Determination of pharmacokinetics of cocaine in sheep by liquid chromatography

Cocaine was administered as 1-, 2-, and 4-mg/kg intravenous bolus doses to each of six sheep. Plasma samples were collected as a function of time and assayed for cocaine using reversed-phase ion-pair HPLC. The assay involved double extraction with ether and UV detection at 229 nm. Using 2 mL of plasma, levels of 1 ng/mL of cocaine can be measured. The concentration versus time data obtained for the plasma samples were analyzed by a "noncompartmental" method. The pharmacokinetic parameters of cocaine in sheep had mean values of 4.0 L/kg, 3.5 L/kg, and 0.29 L X min-1 X kg-1 for Vd, Vdss, and CL respectively. The clearance of cocaine in sheep was much higher than cardiac output. Pulmonary first-pass effect has been suggested as the possible explanation for the large clearance of cocaine in sheep.