Plasma concentrations of clozapine and its metabolites desmethylclozapine and clozapine N-oxide were measured in 61 patients with refractory schizophrenia. Before the initiation of clozapine, each patient was given haloperidol (HL) up to 60 mg/day for at least 4 weeks without improvement. Patients were then given a fixed dose of clozapine 400 mg/day. Patients were assessed with the Brief Psychiatric Rating Scale (BPRS) at baseline before HL therapy, at the end of HL at 6 weeks, before clozapine, and after 6 weeks of clozapine therapy. Clozapine and its metabolites were measured by high-performance liquid chromatography with ultraviolet detection. The mean plasma concentrations of clozapine, desmethylclozapine, and clozapine N-oxide were 598 +/- 314, 281 +/- 140, and 90 +/- 29 ng/ml, respectively. The mean decrease in the total BPRS scores from baseline clozapine to the 6-week treatment period was 11 +/- 4. Clinical improvement was noted to occur in most patients with clozapine plasma levels > 300 ng/ml. Improvement diminished in patients with clozapine plasma levels > 700 ng/ml. The most common adverse effects were sedation and hypersalivation. Significant correlations between plasma clozapine concentrations and adverse side effects were not found.

No abstract

The pharmacokinetic interaction between buspirone and haloperidol was evaluated in schizophrenic patients in two different groups. In both groups, haloperidol doses (10-40 mg/day) remained constant for 6 weeks before the addition of buspirone 10 mg three times daily. Serial blood samples were obtained from the 11 patients in group I at baseline (before addition of buspirone) and after administration for 24 hours. The pharmacokinetic parameters of haloperidol were determined alone and with coadministration of buspirone. In group II, buspirone 10 mg three times daily was added to treatment with haloperidol in 27 patients. Blood samples were obtained before addition of buspirone and at weeks 2 and 6 of treatment with buspirone. Samples were obtained 10 to 12 hours after administration of the evening dose and before the morning dose. Haloperidol and its metabolite, reduced haloperidol (RH), were assayed by means of high-performance liquid chromatography with electrochemical detection. Significant changes in the pharmacokinetic parameters of haloperidol were not found in group I; a mean increase in the half-life (t1/2) of haloperidol from 21.5 to 28.1 hours was observed, but this finding was not statistically significant. Under steady-state conditions, plasma levels of haloperidol in the patients in group II did not change significantly from baseline to week 6. Plasma concentrations of RH remained unaltered in both groups. The results indicate that coadministration of buspirone does not markedly affect the pharmacokinetics or plasma concentrations of haloperidol.

No abstract