Owen J R, Nemeroff C B
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Depress Anxiety. 1998;7 Suppl 1:24-32.
This review critically evaluates recent information on the cytochrome P450 system, with an emphasis on drug interactions involving antidepressant medications, particularly venlafaxine, nefazodone, and mirtazapine.
International literature on the cytochrome P450 system and related drug interactions from 1995-1997 were critically examined.
Venlafaxine, nefazodone, and mirtazapine have different effects on the cytochrome P450 system. In vitro, venlafaxine is a weaker CYP2D6 inhibitor than most of the selective serotonin reuptake inhibitors (SSRIs) by a factor of 1-3 orders of magnitude. In vivo drug interaction studies generally confirm in vitro results. However, some exceptions exist. The clinical significance of such interactions remains unknown. Venlafaxine had minimal or no demonstratable inhibition of CYP1A2, CYP3A4, or CYP2C. Nefazodone is a potent inhibitor of CYP3A4 and is therefore absolutely contraindicated with concurrent administration of terfenadine, astemizole, and cisapride. It is a weak inhibitor of CYP1A2, 3A4, and 2D6. A metabolite of nefazodone, mCPP, is a weak and probably clinically insignificant inhibitor of CYP2D6. Mirtazapine has minimal inhibitory effects on CYP1A2, CYP3A4, and CYP2D6 in vitro. Little is known about its interactions with other drugs.
With the addition of the latest antidepressant medications, the clinician may now choose antidepressants with little liability for drug-drug interactions. Venlafaxine and mirtazapine are associated with a lower risk of clinically significant drug interactions than SSRIs. Nefazodone is a potent inhibitor of CYP3A4 and therefore may not be suitable for all patient populations. It is, however, a much weaker CYP2D6 inhibitor than the SSRIs. More studies are needed to assess more accurately and precisely the risk of such untoward drug-drug interactions with these novel antidepressants, particularly in more diverse ethnic patient populations.
本综述对细胞色素P450系统的最新信息进行批判性评估，重点关注涉及抗抑郁药物的药物相互作用，尤其是文拉法辛、奈法唑酮和米氮平。
对1995年至1997年关于细胞色素P450系统及相关药物相互作用的国际文献进行了批判性审查。
文拉法辛、奈法唑酮和米氮平对细胞色素P450系统有不同影响。在体外，文拉法辛作为CYP2D6抑制剂比大多数选择性5-羟色胺再摄取抑制剂（SSRI）弱1至3个数量级。体内药物相互作用研究一般证实了体外研究结果。然而，也存在一些例外情况。此类相互作用的临床意义尚不清楚。文拉法辛对CYP1A2、CYP3A4或CYP2C的抑制作用极小或无明显抑制作用。奈法唑酮是CYP3A4的强效抑制剂，因此与特非那定、阿司咪唑和顺阿曲库铵同时给药绝对禁忌。它是CYP1A2、3A4和2D6的弱抑制剂。奈法唑酮的一种代谢产物mCPP是CYP2D6的弱抑制剂，可能在临床上无显著意义。米氮平在体外对CYP1A2、CYP3A4和CYP2D6的抑制作用极小。关于它与其他药物的相互作用知之甚少。
随着最新抗抑郁药物的增加，临床医生现在可以选择药物相互作用可能性较小的抗抑郁药。与SSRI相比，文拉法辛和米氮平发生具有临床意义的药物相互作用的风险较低。奈法唑酮是CYP3A4的强效抑制剂，因此可能并不适用于所有患者群体。然而，它作为CYP2D6抑制剂比SSRI弱得多。需要进行更多研究，以更准确、精确地评估这些新型抗抑郁药发生此类不良药物相互作用的风险，尤其是在更多样化的种族患者群体中。
