Cross Sarah A, Perry Caroline M
Wolters Kluwer Health | Adis, Auckland, New Zealand.
Drugs. 2007;67(13):1931-43. doi: 10.2165/00003495-200767130-00012.
Tacrolimus once-daily (OD) is a new oral formulation of the well established immunosuppressant tacrolimus. Tacrolimus OD provided equivalent steady-state systemic tacrolimus exposure to that achieved with standard oral tacrolimus twice daily in stable renal and liver transplant recipients. The two formulations also provided broadly similar steady-state systemic exposure in de novo renal and liver transplant recipients. In a large, randomised, nonblind, multicentre, three-armed, noninferiority trial in de novo renal transplant recipients, the efficacy failure rates (primary endpoint) [any patient who died, experienced graft failure, had a biopsy-confirmed acute rejection or was lost to follow-up] of tacrolimus OD (14.0%) and standard tacrolimus (15.1%) were noninferior to that of ciclosporin (cyclosporine) microemulsion (17.0%) at 1 year, when each was given in conjunction with corticosteroids, mycophenolate mofetil and basiliximab induction. Data from a pharmacokinetic study suggests that tacrolimus OD has similar efficacy to standard tacrolimus in de novo liver transplant recipients over 6 weeks of treatment. In noncomparative 2-year trials, tacrolimus OD was effective in stable renal and liver transplant recipients converted to tacrolimus OD from standard tacrolimus. The overall tolerability profile of tacrolimus OD appears to be similar to that of standard tacrolimus in de novo and stable renal and liver transplant patients.
他克莫司每日一次（OD）是成熟的免疫抑制剂他克莫司的一种新的口服制剂。在稳定的肾移植和肝移植受者中，他克莫司OD的稳态全身他克莫司暴露量与标准口服他克莫司每日两次所达到的暴露量相当。在初次肾移植和肝移植受者中，这两种制剂也提供了大致相似的稳态全身暴露量。在一项针对初次肾移植受者的大型、随机、非盲、多中心、三臂、非劣效性试验中，当他克莫司OD（14.0%）和标准他克莫司（15.1%）分别与皮质类固醇、霉酚酸酯和巴利昔单抗诱导剂联合使用时，1年时的疗效失败率（主要终点）[任何死亡、经历移植失败、经活检证实有急性排斥反应或失访的患者]不劣于环孢素微乳剂（17.0%）。一项药代动力学研究的数据表明，在治疗6周以上的初次肝移植受者中，他克莫司OD与标准他克莫司疗效相似。在非对照的2年试验中，他克莫司OD对从标准他克莫司转换为他克莫司OD的稳定肾移植和肝移植受者有效。在初次及稳定的肾移植和肝移植患者中，他克莫司OD的总体耐受性似乎与标准他克莫司相似。
