The relationship between perphenazine plasma levels and clinical response in acute schizophrenia.

1. Twelve patients with schizophrenia according to RDC participated in a double-blind study, comparing two dose levels of perphenazine, 16 or 32 mg, during four weeks. 2. The patients were assessed with a subscale to CPRS and global scores, measuring improvement of regular intervals during four weeks. 3. Blood samples for assay of plasma perphenazine were collected once a week. 4. These results are in many respects in accordance with earlier published data with perphenazine, that is a good clinical response is achieved with a plasma concentration of perphenazine between 1-5 nmol/L. 5. No incidence of severe adverse symptoms were observed.

Effect of simultaneous treatment with low doses of perphenazine on plasma and urine concentrations of nortriptyline and 10-hydroxynortriptyline.

Plasma levels of nortriptyline and perphenazine were measured in six patients on continuous nortriptyline treatment before, during and after oral administration of perphenazine 4 mg t.i.d. In four patients the plasma levels of the conjugated and unconjugated principal metabolite 10-hydroxynortriptyline were also measured. Urinary excretion of conjugated and unconjugated 10-hydroxynortriptyline and plasma levels of perphenazine were determined in all six patients. During treatment with perphenazine two patients showed a slight increase in the plasma level of nortriptyline. The changes in metabolite excretion rate were inconclusive. Thus, there did not appear to be any important pharmacokinetic interaction between the two drugs at the doses used, which were normal therapeutic doses. The previously reported inhibitory effect of perphenazine on the metabolism of nortriptyline probably depended therefore, either on administration of a higher dose of perphenazine, or on treatment in the reverse sequence--a single dose of nortriptyline was given to patients already receiving perphenazine.

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.