Heeringa M, Beurskens R, Schouten W, Verduijn M M
Netherlands Pharmacovigilance Foundation Lareb, 's Hertogenbosch, The Netherlands.
Pharm World Sci. 1999 Oct;21(5):243-4. doi: 10.1023/a:1008748110692.
Selective serotonin reuptake inhibitors can be added to clozapine therapy in order to treat remaining negative symptoms and obsessive compulsive symptoms. The present case report describes a 44-year-old man exhibiting extremely elevated plasma levels of clozapine after the addition of fluvoxamine, up to 4160 mcg/l. The elevated plasma levels of clozapine, which were discovered 6 months after the SSRI was added, is likely to be caused by a drug-drug interaction. Clozapine is a substrate of CYP 1A2 and is predominantly metabolised in the liver. Of the SSRIs, fluvoxamine is one of the most potent inhibitors of the isoenzyme CYP 1A2. This case serves to emphasise the need for continuous attention to drug-drug interactions, especially when they might be easily overlooked due to the lack of clear symptoms.
选择性5-羟色胺再摄取抑制剂可添加到氯氮平治疗中,以治疗残留的阴性症状和强迫症状。本病例报告描述了一名44岁男性,在添加氟伏沙明后,氯氮平血浆水平极度升高,高达4160微克/升。在添加选择性5-羟色胺再摄取抑制剂6个月后发现的氯氮平血浆水平升高,可能是由药物相互作用引起的。氯氮平是细胞色素P450 1A2(CYP 1A2)的底物,主要在肝脏中代谢。在选择性5-羟色胺再摄取抑制剂中,氟伏沙明是同工酶CYP 1A2最有效的抑制剂之一。本病例强调了持续关注药物相互作用的必要性,尤其是当它们可能因缺乏明显症状而容易被忽视时。