An open study of tolerability and pharmacokinetics of raclopride extended release capsules in psychiatric patients: a Canadian study.

The tolerability and pharmacokinetics of raclopride extended release (ER) capsules have been evaluated after a single oral dose and at steady state, with 3 different daily doses in 4 male patients requiring neuroleptic treatment. In this 3-week open study, the drug was administered to patients in increasing bid doses of 8 mg, 12 mg and 16 mg, respectively, for each 1-week treatment period, following a 1-week placebo washout. With this limited number of patients, assessments of clinical chemistry, hematology, cardiovascular variables and adverse symptoms suggest that raclopride is safe and well-tolerated in the group studied. The administration of repeated doses of raclopride showed linear pharmacokinetics based on parameter values which are either constant (effective elimination half-life, total plasma clearance, and dose-normalized area under the plasma concentration-time curve) or varying proportionally (trough plasma concentration, peak plasma concentration, average plasma concentration and the area under the plasma concentration-time curve for a dosage interval at steady state) with the doses. The linear 1-compartment open model with zero-order absorption was the most appropriate pharmacokinetic model describing the raclopride plasma concentration profile after a single 8 mg dose of raclopride ER capsules. The ER formulation reduced the fluctuation between peak and trough plasma drug concentrations which has been reported before with instant release dosage forms. In this study, the increase of plasma prolactin concentrations above the normal limit was transient and returned to normal levels. Although the plasma prolactin concentration tended to increase with the drug dose, no direct relationship between raclopride dose and prolactin plasma concentrations was found. The correlation of plasma prolactin response with the plasma raclopride concentration showed a low level of hysteresis.