Clinical pharmacokinetic studies of perphenazine

A gas‐chromatographic method was used for the study in man of the kinetics of perphenazine (PPZ) and its sulphoxide metabolite (PPZ‐SO). Various forms of PPZ administration were applied in eighteen schizophrenic patients and four healthy volunteers. Following an i.v. dose of 5 or 6 mg a considerable fluctuation in the plasma concentration was noted before the exponential elimination phase. The average terminal half‐life of PPZ was approximately 9.5 hours. PPZ‐SO showed up quickly but in low concentrations. After an oral dose of 6 mg no PPZ was detected in plasma and PPZ‐SO only as traces. During continuous oral medication, 12 mg three times daily, a low systemic availability and a high PPZ‐SO/PPZ ratio was found suggesting a marked first pass effect. PPZ‐enanthate given i.m. fortnightly resulted in PPZ‐ levels comparable to those seen after continuous oral medication, but PPZ‐SO concentration were much lower. No accumulation was observed. The systemic clearance rate (average approximately 100 1/h) was the same after PPZ‐enanthate i.m. and PPZ i.v., but varied three‐fold individually. Side effects were mostly, but not always, registered concomitant with high plasma levels of PPZ.