Junge G, Dumortier T, Schwende H, Fung J
Department of Integrated Hospital Care (IHC), Basel, Switzerland.
Transplant Proc. 2013 Jun;45(5):1979-80. doi: 10.1016/j.transproceed.2013.02.102.
Everolimus (EVR) is a semi-synthetic mammalian target of rapamycin inhibitor currently under development for liver transplantation (LTx) in combination with reduced exposure tacrolimus (rTAC). The relative potency of EVR was assessed in order to generate evidence for concomitant EVR+rTAC exposure in LTx recipients (LTxR). Twelve month data from study H2304 (NCT00622869), a 24-month, randomized, multicenter study in 719 de novo LTxR comparing EVR+rTAC to standard TAC demonstrated superior renal function and comparable efficacy, including fewer and less severe biopsy proven acute rejections with EVR+rTAC. Relative potency (p) of EVR was defined as factor by which the effect of 1 ng/mL of EVR must be multiplied to get comparable immunosuppression as with TAC: p = (TACcon - TACred)/EVRred. Relative efficacy of EVR in 4 different subpopulatlons was consistently 0.64, 0.60, 0.69, and 0.62, respectively. This assessment determined the relative potency of EVR as 0.64 compared to TAC in LTx indicating that EVR and TAC are not equipotent per ng/mL exposure. Knowledge about relative potency will help to rationalize co-exposure of EVR and TAC.
依维莫司（EVR）是一种半合成的哺乳动物雷帕霉素靶蛋白抑制剂，目前正与低剂量他克莫司（rTAC）联合用于肝移植（LTx）的研究。评估了依维莫司的相对效价，以便为肝移植受者（LTxR）同时使用依维莫司+rTAC提供依据。研究H2304（NCT00622869）为期24个月，是一项针对719例初发肝移植受者的随机、多中心研究，比较了依维莫司+rTAC与标准他克莫司（TAC），其12个月的数据表明，依维莫司+rTAC组肾功能更优，疗效相当，包括经活检证实的急性排斥反应更少、更轻。依维莫司的相对效价（p）定义为使1 ng/mL依维莫司的效应乘以该因子后可获得与他克莫司相当的免疫抑制效果：p =（TACcon - TACred）/EVRred。依维莫司在4个不同亚组中的相对疗效分别始终为0.64、0.60、0.69和0.62。该评估确定依维莫司在肝移植中相对于他克莫司的相对效价为0.64，这表明每ng/mL暴露量下依维莫司和他克莫司并非等效。了解相对效价将有助于合理确定依维莫司和他克莫司的联合暴露量。
