Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand.
Pharmacy Department, Siriraj Hospital, Bangkok, 10700, Thailand.
Int J Clin Pharm. 2019 Aug;41(4):1047-1055. doi: 10.1007/s11096-019-00848-w. Epub 2019 May 25.
Background The effects of mycophenolic acid exposure in the early period after transplantation on clinical outcomes have been reported; however, mycophenolic acid exposure in the early period after transplantation in Asian kidney transplant recipients who receive 1.5 g/d mycophenolate mofetil has never been investigated. Objective To determine mycophenolic acid exposure on day 3 post-transplantation in kidney transplant recipiens who receive 1.5 g/d mycophenolate mofetil. The effects of the reduced renal function on mycophenolic acid area under the concentration-time curve (AUC) and the achievement of the target AUC on the incidence of biopsy proven acute rejection during the first month post-transplantation were also evaluated. Setting A university hospital Method Blood samples and 24-h urine were collected on day 3 post-transplantation. Main outcome measures The mycophenolic acid AUC was calculated by linear trapezoidal rule and compared with the target of 45 mgh/L. Results Of 42 Thai kidney transplant recipiens, the mean mycophenolic acid AUC of 45.1 mgh/L (SD 14.7) was comparable to the AUC target (P = 0.962). Significant differences of the mycophenolic acid AUC were observed between patients with urine output of < 2400 mL and those with urine output ≥ 2400 mL (35.3 ± 6.6 and 47.4 ± 15.2, respectively; P = 0.002), and between patients with 24-h measured CrCl < 25 mL/min and those with CrCl ≥ 25 mL/min (38.0 (29.0, 42.2) and 49.2 ± 14.0, respectively; P = 0.017). Proportions of overall biopsy proven acute rejection among patients with mycophenolic acid AUC of < 45 and ≥ 45 mgh/L were comparable (20.0% and 23.5%, respectively; P = 1.000). Conclusions After the starting dosage of 1.5 g/d mycophenolate mofetil, the mean mycophenolic acid AUC on day 3 post-kidney transplantation is comparable with the target of 45 mgh/L. Severely reduced renal function significantly influences mycophenolic acid exposure.
已有研究报道了移植后早期麦考酚酸暴露对临床结局的影响，但在接受 1.5g/d 吗替麦考酚酯的亚洲肾移植受者中，尚未对移植后早期麦考酚酸暴露进行研究。目的：确定接受 1.5g/d 吗替麦考酚酯的肾移植受者移植后第 3 天的麦考酚酸暴露情况。还评估了肾功能减退对麦考酚酸浓度-时间曲线下面积（AUC）和移植后第 1 个月活检证实急性排斥反应发生率目标 AUC 的影响。地点：一所大学医院。方法：在移植后第 3 天采集血样和 24 小时尿液。主要观察指标：采用线性梯形法则计算麦考酚酸 AUC，并与 45mg·h/L 的目标值进行比较。结果：在 42 例泰国肾移植受者中，平均麦考酚酸 AUC 为 45.1mg·h/L（SD 14.7），与 AUC 目标值（P=0.962）相当。尿量<2400mL 和≥2400mL 的患者之间（分别为 35.3±6.6 和 47.4±15.2；P=0.002）以及 24 小时内测量的 CrCl<25mL/min 和≥25mL/min 的患者之间（分别为 38.0（29.0，42.2）和 49.2±14.0；P=0.017）的麦考酚酸 AUC 存在显著差异。AUC<45 和≥45mg·h/L 的患者中，总活检证实急性排斥反应的比例相当（分别为 20.0%和 23.5%；P=1.000）。结论：在起始剂量为 1.5g/d 吗替麦考酚酯后，肾移植后第 3 天的平均麦考酚酸 AUC 与 45mg·h/L 的目标值相当。严重的肾功能减退显著影响麦考酚酸的暴露。
