Colombo D, Lunardon L, Bellia G
Novartis Farma S.p.A., Origgio, Varese, Italy ; Marchesi Hospital, Inzago, Milan, Italy.
Department of Pathophysiology and Transplantation, University of Milan, I.R.C.C.S. Foundation, Cà Granda Ospedale Maggiore Policlinico, Milan, Italy.
J Toxicol. 2014;2014:145325. doi: 10.1155/2014/145325. Epub 2014 Jan 12.
Cyclosporine (CyA) is a well-known immunosuppressant with a narrow therapeutic window. Its bioavailability is affected by many other traditional drugs and herbal extracts. Cytochrome P-450 isoenzymes CYP3A4 and CYP3A5 and protein P-glycoprotein (P-gp) are involved in CyA bioavailability. Interactions of CyA with herbal extracts are not well known, but, given their increased concomitant use, it is important to know which extracts, many of which are commonly self-prescribed, can affect CyA blood concentrations. Decreased CyA blood concentration has been shown with St John's wort in case reports and, in vivo animal studies, with ginger, liquorice, scutellariae radix, and quercetin. Increased CyA concentration has been reported in patients with grapefruit juice, chamomile, or berberine, and with cannabidiol or resveratrol in animal studies. Effects of Echinacea and Serenoa repens on CyA levels have not been shown consistently, but concomitant use should be avoided. Although findings from animal studies cannot be directly translated into humans, avoiding concomitant use of herbal extracts is prudent until human clinical studies have ruled out any possible interaction. Clinicians should interview their patients carefully about their use of herbal supplements before CyA administration, and those receiving CyA should be warned about possible interactions between herbal preparations and CyA.
环孢素(CyA)是一种众所周知的免疫抑制剂,治疗窗较窄。其生物利用度受许多其他传统药物和草药提取物的影响。细胞色素P-450同工酶CYP3A4和CYP3A5以及蛋白P-糖蛋白(P-gp)参与环孢素的生物利用度。环孢素与草药提取物的相互作用尚不清楚,但考虑到它们联合使用的情况增多,了解哪些提取物(其中许多是患者自行用药)会影响环孢素血药浓度很重要。病例报告显示,圣约翰草可降低环孢素血药浓度,体内动物研究表明,生姜、甘草、黄芩和槲皮素也有此作用。有报道称,葡萄柚汁、洋甘菊或小檗碱可使患者体内环孢素浓度升高,动物研究表明,大麻二酚或白藜芦醇也有此作用。紫锥菊和锯叶棕对环孢素水平的影响尚未得到一致证实,但应避免联合使用。尽管动物研究结果不能直接类推到人类,但在人体临床研究排除任何可能的相互作用之前,谨慎起见应避免联合使用草药提取物。临床医生在给予环孢素之前,应仔细询问患者使用草药补充剂的情况,并且应警告接受环孢素治疗的患者注意草药制剂与环孢素之间可能存在的相互作用。