Bioequivalence of clozapine orally disintegrating 100-mg tablets compared with clozapine solid oral 100-mg tablets after multiple doses in patients with schizophrenia.
BACKGROUND
This study compared the bioequivalence of FazaClo (clozapine orally disintegrating tablets) 100 mg to Clozaril (clozapine standard oral tablets) 100 mg after multiple doses in patients with schizophrenia.


METHODS
This was a randomized, open-label, multiple-dose study in which patients with schizophrenia received FazaClo or Clozaril 100 mg twice daily for 5 days before crossing over to the alternate therapy. Blood samples were obtained at regular intervals during and after the completion of treatment, and standard pharmacokinetic parameters were calculated. Safety and patient satisfaction with FazaClo were also assessed.


RESULTS
Thirty-six patients were enrolled, of whom 33 completed the study and 30 were included in the steady-state analyses. All pharmacokinetic parameters for clozapine and desmethylclozapine (the major metabolite of clozapine) were similar between FazaClo and Clozaril in both the completer and steady-state populations. Geometric mean values for steady-state maximum and minimum concentrations and area under the plasma concentration-time curve for FazaClo were all within 95-105% of those for Clozarilwell within the range considered by the US FDA as acceptable for bioequivalence (80-125%). Patients also expressed a high level of satisfaction with the FazaClo orally disintegrating tablet formulation.


CONCLUSIONS
FazaClo produced pharmacokinetic profiles almost identical to those of Clozaril. This should provide clinicians with reassurance that patients who receive FazaClo will achieve plasma drug concentrations similar to those produced by the same daily dose of Clozaril, and that no cross-titration is necessary when switching from one of these clozapine formulations to the other.
Golden
Gil
G
Medical Affairs, Azur Pharma, Inc., Philadelphia, Pennsylvania 19103, USA. gil.golden@azurpharma.com
Honigfeld
Gilbert
G
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D019540:Area Under Curve; D003024:Clozapine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D006970:Disorders of Excessive Somnolence / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D016568:Drugs, Generic / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D005260:Female; D006207:Half-Life; D006801:Humans; D007415:Intestinal Obstruction / Q000139:chemically induced; D007421:Intestine, Small / Q000187:drug effects / Q000473:pathology; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D010352:Patient Dropouts / Q000706:statistics & numerical data; D017060:Patient Satisfaction; D012559:Schizophrenia / Q000188:drug therapy* / Q000378:metabolism; D013546:Sweating / Q000187:drug effects; D013607:Tablets; D013810:Therapeutic Equivalency
D014150:Antipsychotic Agents; D016568:Drugs, Generic; D013607:Tablets; C058272:norclozapine; D003024:Clozapine