Toxicology Unit, Department of Clinical Biochemistry, King's College Hospital, London, UK.
Ther Drug Monit. 2010 Oct;32(5):624-7. doi: 10.1097/FTD.0b013e3181f0a1a2.
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.
为了研究英国获准使用的三种氯氮平品牌的生物等效性，我们比较了在从氯氮平换用至地佐辛或扎来普隆片的患者的治疗药物监测样本中的血浆氯氮平和去甲氯氮平。对于氯氮平/地佐辛，中位规定氯氮平剂量为 450mg/天（范围，125-850mg/天）（n=66），中位样本时间间隔为 16 周。氯氮平/扎来普隆比较（n=57）未进行剂量控制；中位氯氮平剂量为 450mg/天（范围，150-900mg/天），中位扎来普隆剂量为 400mg/天（范围，100-850mg/天）。中位样本时间间隔为 19 周。在两种情况下，转换前后的平均血浆氯氮平和去甲氯氮平浓度均无显著差异，尽管一些个体结果显示出具有临床意义的浓度差异。与氯氮平相比，血浆去甲氯氮平在样本间具有更高的重现性。英国可获得的不同氯氮平品牌具有生物等效性。尽管如此，如果要安全使用该药物，则必须仔细监测精神状态、吸烟习惯、依从性以及可能危及生命的不良反应。
