title: The Elimination Rate after Clozapine Overdose in Chinese Schizophrenia Patients: A Population Pharmacokinetics Model Study.
abstract: BACKGROUND
  The prescribing of clozapine in China is common because of its outstanding efficacy and low price. There have been many cases of clozapine overdose in China. However, studies about the pharmacokinetics after overdose in the Chinese have rarely been reported. Population pharmacokinetics (PopPK) can analyze sparse data, and it is appropriate to compute clozapine pharmacokinetics after overdose.
  
  
  METHODS
  There were 47 clozapine overdose cases. We constructed a single-compartment first-order elimination PopPK model. We also considered some covariates that can influence the pharmacokinetics parameters.
  
  
  RESULTS
  21 cases were included in the analysis. When the reported toxic dosage was 3,740 mg, the elimination rate constant of the population was 0.0258(h(-1)). The elimination half-life was 26.9 h. The coefficient of random variation was 17%.
  
  
  CONCLUSIONS
  PopPK can solve the problem of sparse data after overdose. The area under the concentration-time curve after clozapine overdose exhibited the "two peaks phenomenon." The reported toxic dosage could impact clozapine elimination after overdose. Delayed absorption of clozapine is the best explanation for this finding.
authors.affiliation: Beijing Key Laboratory of Mental Disorders, Department of Psychiatry, Beijing Anding Hospital, Capital Medical University, Beijing, China.
authors.forename: A-N
authors.initials: AN
authors.lastname: Li
authors.affiliation: Beijing Key Laboratory of Mental Disorders, Department of Psychiatry, Beijing Anding Hospital, Capital Medical University, Beijing, China.
authors.forename: F
authors.initials: F
authors.lastname: Dong
authors.affiliation: Beijing Key Laboratory of Mental Disorders, Department of Psychiatry, Beijing Anding Hospital, Capital Medical University, Beijing, China.
authors.forename: J-L
authors.initials: JL
authors.lastname: He
authors.affiliation: Guangzhou Brain Hospital, Guangzhou Huiai Hospital, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: D-W
authors.initials: DW
authors.lastname: Shang
authors.affiliation: Beijing Key Laboratory of Mental Disorders, Department of Psychiatry, Beijing Anding Hospital, Capital Medical University, Beijing, China.
authors.forename: W
authors.initials: W
authors.lastname: Guo
authors.affiliation: Beijing Key Laboratory of Mental Disorders, Department of Psychiatry, Beijing Anding Hospital, Capital Medical University, Beijing, China.
authors.forename: W-B
authors.initials: WB
authors.lastname: Li
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, China.
authors.forename: W
authors.initials: W
authors.lastname: Lu
authors.affiliation: Beijing Key Laboratory of Mental Disorders, Department of Psychiatry, Beijing Anding Hospital, Capital Medical University, Beijing, China.
authors.forename: C-Y
authors.initials: CY
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D044466:Asian People; D002681:China; D003024:Clozapine / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D062787:Drug Overdose / Q000378:metabolism*; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D012559:Schizophrenia / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine