STEADY-STATE SERUM KINETICS OF ZOTEPINE

The steady-state serum kinetics of zotepine, an antipsychotic drug, were studied in 59 psychiatric in-patients receiving 50-500 mg/day (mean 215 mg/day) of the drug. There was a 26-fold inter-individual variation in the concentration/dose ratios (C/D ratios: ng/ml/mg/kg), which ranged from 2.4 to 62.2 (mean 13.2). The smokers (n = 37) had significantly lower C/D ratios (mean +/- SD: 9.7 +/- 7.0 vs 19.0 +/- 15.5, p < 0.01), while the patients co-administered benzodiazepines (n = 14) had significantly higher C/D ratios (19.6 +/- 12.5 vs 11.2 +/- 10.9, p < 0.01) than the others. There was no significant relationship between the C/D ratios and age or gender. In the 24 cases where the dose was fixed at 100 mg/day in the first week and at 200 mg/day for the next 3 weeks, no significant difference was found in the mean C/D ratios during the 4 weeks. The present study thus suggests a large inter-individual variation in the metabolism of zotepine, and that smoking enhances, and co-administration of benzodiazepines inhibits, the metabolism. Age and gender do not affect the kinetics of the drug. The results also suggest no dose-dependent kinetics and no enzyme-inducing effect of the drug.