title: Evaluation of three dosing models for the prediction of steady-state trough clozapine concentrations.
abstract: OBJECTIVE
  Therapeutic drug monitoring of clozapine may be useful for the clinical management of schizophrenic patients treated with this atypical antipsychotic drug. The aim of our study was the evaluation of three models for the prediction of steady-state trough clozapine concentration.
  
  
  METHODS
  The trough serum concentrations of clozapine and norclozapine were determined by high-performance liquid chromatography in 296 samples from a group of 21 schizophrenic patients selected for their good therapeutic compliance. Also, the predicted clozapine concentrations were estimated by applying the models of Oyewumi et al. (Ther Drug Monit 1995; 17: 137), Perry et al. (Biol Psychiatry 1998; 44: 733) and Rostami-Hodjegan et al. (J Clin Psychopharmacol 2004; 24: 70).
  
  
  RESULTS
  The efficiency for the accurate estimation of clozapine concentrations as subtherapeutic (<240 ng/mL), therapeutic (240-750 ng/mL) or supratherapeutic (>750 ng/mL), using the models of Oyewumi et al., Perry et al., and Rostami-Hodjegan et al., was 82%, 71% and 77% respectively.
  
  
  CONCLUSIONS
  The predictive model of Oyewumi et al., which shows an easy calculation way and the greater diagnostic efficiency, may be of clinical value for the prediction of clozapine concentration or the dose required to achieve a specified concentration.
authors.affiliation: Hospital Psiquiátrico de Conxo, Santiago de Compostela, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Paz
authors.forename: Lorena
authors.initials: L
authors.lastname: Bouzas
authors.forename: Jesús
authors.initials: J
authors.lastname: Hermida
authors.forename: Julio
authors.initials: J
authors.lastname: Brenlla
authors.forename: J Carlos
authors.initials: JC
authors.lastname: Tutor
mesh_terms: D000328:Adult; D000368:Aged; D003024:Clozapine / Q000008:administration & dosage* / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods / Q000592:standards; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011237:Predictive Value of Tests; D012907:Smoking / Q000097:blood
chemical_list: D003024:Clozapine