Concentrations of mycophenolic acid and glucuronide metabolites under concomitant therapy with cyclosporine or tacrolimus.
Concentrations of mycophenolic acid and glucuronide metabolites under concomitant therapy with cyclosporine or tacrolimus.
复制标题
与环孢素或他克莫司联合治疗时麦考酚酸和葡萄糖醛酸代谢物的浓度。
DOI：
10.1097/ftd.0b013e3180318c35
复制
发表时间：
2007
影响因子：
2.5
通讯作者：
Akhlaghi,Fatemeh
中科院分区：
文献类型：
--
作者：
Patel,ChiragG;Harmon,Matthew;Gohh,ReginaldY;Akhlaghi,Fatemeh
Mycophenolate mofetil [MMF, the prodrug of mycophenolic acid (MPA)] is usually administered at double doses with cyclosporine than with tacrolimus because it is believed that MPA exposure is lower during cyclosporine therapy. This study aimed to compare 12 hour, steady-state concentration-time profiles of MPA and its phenol-and acyl-glucuronide metabolites (MPAG and AcMPAG, respectively) in stable kidney transplant recipients maintained either on cyclosporine (n= 12) or tacrolimus (n= 12). During the absorption phase in the cyclosporine group, dose-normalized concentrations of total and free MPA were significantly higher but the overall area under the concentration-time curve (AUC 0-12) was not significantly different. Additionally, exposure to AcMPAG was higher in the cyclosporine group (P< 0.05). Ten of 12 patients in the cyclosporine group were on ketoconazole therapy; however, the exposure to MPA or MPAG was not different when MMF was given orally to Sprague-Dawley rats with or without ketoconazole. In conclusion, cyclosporine modulates the disposition of MPA and metabolites differently from tacrolimus; however, patients on cyclosporine may not require double doses of MMF to achieve the same exposure.
