Pharmacokinetic studies of antipsychotics in healthy volunteers versus patients.
In clinical trials of dopamine-blocking antipsychotics, significant adverse events may occur in healthy volunteers at dose levels that are well tolerated by schizophrenic patients. Because of these differences in tolerability, bioequivalence and pharmacokinetic studies of antipsychotics should be performed in schizophrenic patients rather than in healthy volunteers. When clozapine is the drug being investigated, pharmacokinetic and bioequivalence studies should be carried out in real-life dosage conditions because the half-life of clozapine increases with multiple doses. Under real-life conditions, the evaluation of multiple doses of clozapine in a population of schizophrenic patients can provide direct therapeutic relevance to bioavailability findings. This article discusses patient recruitment and informed consent in pharmacokinetic trials of schizophrenia, issues in studying antipsychotic agents in healthy volunteers versus schizophrenic patients, and a bioequivalency study of Clozaril (Novartis Pharmaceuticals) and generic clozapine (Creighton [Sandoz]) in schizophrenic patients.
Cutler
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NR
California Clinical Trials, Beverly Hills, USA.
D014150:Antipsychotic Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002986:Clinical Trials as Topic / Q000592:standards; D003024:Clozapine / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D018492:Dopamine Antagonists / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D017277:Drug Approval; D004361:Drug Tolerance; D016568:Drugs, Generic / Q000493:pharmacokinetics; D006207:Half-Life; D006801:Humans; D007258:Informed Consent; D008297:Male; D018579:Patient Selection; D012559:Schizophrenia / Q000188:drug therapy* / Q000378:metabolism; D013810:Therapeutic Equivalency; D014481:United States; D014486:United States Food and Drug Administration / Q000592:standards
D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D016568:Drugs, Generic; D003024:Clozapine