Linear pharmacokinetics of haloperidol in the rat

Pharmacokinetics of haloperidol in the rat following intravenous bolus doses of 0·5, 1·0, and 2·5 mg kg−1, respectively, were investigated. It was found that haloperidol was a high extraction ratio drug with a total blood clearance averaging 83 ml min−1 kg−1. The volumes of distribution were large with a mean of 5·5 1 kg−1 (Vc), 11·11 kg−1 (Vβ), and 9·61 kg−1 (Vss), respectively. The terminal half‐life was 1·5h. The disposition kinetics of haloperidol was found to be linear over the dose range studied. After constant intravenous infusions of haloperidol by different infusion rates during 12h, steady‐state levels were reached in the blood. The measured steady‐state blood concentrations were consistent with those predicted by a biexponential infusion model based on the parameters obtained from the intravenous bolus study. The total blood clearance at steady‐state was concentration‐independent within the investigated range of 5 to 20 ng ml−1.