Plasma clozapine and norclozapine in patients prescribed different brands of clozapine (Clozaril, Denzapine, and Zaponex).
To investigate the bioequivalence of the three clozapine brands licensed in the United Kingdom, we compared plasma clozapine and norclozapine in therapeutic drug monitoring samples from patients switched from Clozaril to either Denzapine or Zaponex tablets. For Clozaril/Denzapine, the median prescribed clozapine dose was 450 mg/day (range, 125-850 mg/day) (n = 66) and the median time between samples was 16 weeks. The Clozaril/Zaponex comparison (n = 57) was not dose-controlled; the median Clozaril dose was 450 mg/day (range, 150-900 mg/day) and the median Zaponex dose 400 mg/day (range, 100-850 mg/day). The median time between samples was 19 weeks. There was no significant difference in mean plasma clozapine and norclozapine concentration before and after switching in either case, although some individual results showed clinically relevant concentration differences. Plasma norclozapine showed greater reproducibility between samples than clozapine. The different brands of clozapine available in the United Kingdom show bioequivalence. Nevertheless, careful monitoring of mental state, smoking habit, adherence, and of possible life-threatening adverse effects is mandatory if the drug is to be used safely.
Couchman
Lewis
L
Toxicology Unit, Department of Clinical Biochemistry, King's College Hospital, London, UK. lewis.couchman@nhs.net
Morgan
Phillip Edgar
PE
Spencer
Edgar Pathrose
EP
Johnston
Atholl
A
Flanagan
Robert James
RJ
D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D003024:Clozapine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D012907:Smoking / Q000378:metabolism; D013810:Therapeutic Equivalency
D014150:Antipsychotic Agents; C058272:norclozapine; D003024:Clozapine