Patel Pranav, Patel Hitesh, Panchal Shital, Mehta Tejal
Department of Pharmaceutics, K.B. Raval College of Pharmacy, Shertha, Gandhinagar, Gujarat, India.
Int J Pharm Investig. 2012 Oct;2(4):169-75. doi: 10.4103/2230-973X.106981.
Tacrolimus (FK 506) is a potent macrolide lactone immunosuppressive agent used for prophylaxis of organ rejection after transplantation and graft-versus-host disease after bone marrow transplantation in patients. Moreover, tacrolimus is a drug of choice in the treatment of atopic dermatitis for decreasing side effects associated with the use of topical corticosteroids. In spite of its success in ensuring graft survival, therapeutic use of tacrolimus is complicated due to its narrow therapeutic index (between 5 and 15 ng/ml). Tacrolimus has a large inter-/intra-patient variability in pharmacokinetics profile and a poor oral bioavailability because of its poor solubility, P-gp efflux, marked pre-systemic metabolism by CYP3A in the enterocytes and liver first pass effect. Several formulation approaches such as oily solution, solid dispersions, complexation with cyclodextrins, liposomes etc., have been investigated to improve oral delivery of FK 506. In this review, we have discussed various formulation approaches that have been undertaken by various researchers to solve the problems related to the drug delivery of tacrolimus.
他克莫司（FK 506）是一种强效大环内酯类免疫抑制剂，用于预防移植后器官排斥反应以及患者骨髓移植后的移植物抗宿主病。此外，他克莫司是治疗特应性皮炎的首选药物，可减少与外用糖皮质激素使用相关的副作用。尽管他克莫司在确保移植物存活方面取得了成功，但其治疗应用因治疗指数狭窄（5至15 ng/ml）而变得复杂。他克莫司在患者间/患者内的药代动力学特征存在很大差异，且口服生物利用度差，这是由于其溶解度低、P-糖蛋白外排、肠细胞和肝脏中CYP3A显著的首过代谢以及肝脏首过效应。为改善FK 506的口服给药，人们研究了多种制剂方法，如油溶液、固体分散体、与环糊精络合、脂质体等。在本综述中，我们讨论了不同研究人员为解决与他克莫司药物递送相关问题所采用的各种制剂方法。
