Vella J P, Sayegh M H
Laboratory of Immunogenetics and Transplantation, Brigham & Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Am J Kidney Dis. 1998 Feb;31(2):320-3. doi: 10.1053/ajkd.1998.v31.pm9469504.
The favorable safety profile of the newer antidepressant drugs recently introduced has lead to their increased use in transplant recipients. These new agents are a chemically diverse group of compounds that have selective serotonin reuptake inhibitory properties. Most of these medications inhibit one or more hepatic microsomal cytochrome p450 isoenzymes. Because cyclosporine is metabolized predominantly by CYP3A3/4 isoenzymes, inhibition of this system can lead to the buildup of toxic levels. Two case reports of cyclosporine toxicity attributable to interactions with the novel antidepressants nefazodone and fluvoxamine are presented. The serum creatinine and whole blood cyclosporine levels were found to be elevated at a routine clinic visit. Although it was subsequently possible to reduce the dose of cyclosporine by between 33% and 50%, the frequency of blood draws and consultations was greatly increased in both patients over several weeks, resulting in considerable patient anxiety. Interestingly, both nefazodone and fluvoxamine are known to potently inhibit the CYP3A3/4 isoenzymes. It is concluded that the introduction of a novel antidepressant to a cyclosporine-treated allograft recipient may be complicated by cyclosporine toxicity. Intensive monitoring of the serum creatinine and cyclosporine level is indicated under such circumstances, with dose reductions performed as indicated.
最近引入的新型抗抑郁药物良好的安全性使其在移植受者中的使用有所增加。这些新药是一组化学性质各异的化合物，具有选择性5-羟色胺再摄取抑制特性。这些药物大多会抑制一种或多种肝微粒体细胞色素P450同工酶。由于环孢素主要由CYP3A3/4同工酶代谢，抑制该系统会导致毒性水平升高。本文报告了两例因与新型抗抑郁药奈法唑酮和氟伏沙明相互作用而导致环孢素中毒的病例。在一次常规门诊就诊时发现血清肌酐和全血环孢素水平升高。尽管随后有可能将环孢素剂量减少33%至50%，但在几周内两名患者的采血和会诊频率都大大增加，导致患者相当焦虑。有趣的是，已知奈法唑酮和氟伏沙明都会强力抑制CYP3A3/4同工酶。得出的结论是，给接受环孢素治疗的同种异体移植受者引入新型抗抑郁药可能会因环孢素中毒而变得复杂。在这种情况下，建议密切监测血清肌酐和环孢素水平，并根据需要减少剂量。
