From the Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Exp Clin Transplant. 2020 Aug;18(4):485-490. doi: 10.6002/ect.2020.0041. Epub 2020 Jun 2.
The aim of this study was to evaluate recipient safety, tolerability, and pharmacokinetics of mycophenolate mofetil suspension compared with mycophenolate mofetil capsules as part of induction therapy after living-donor liver transplant.
Between July 2017 and April 2019, we retrospectively enrolled 20 adult primary living-donor liver transplant recipients. Recipients were divided into 3 groups: group 1 received mycophenolate mofetil suspension of 3000 mg (n = 6), group 2 received 3000 mg mycophenolate mofetil via opened capsules (n = 8), and group 3 received mycophenolate mofetil suspension of 2000 mg (n = 6). Administration was started on postoperative day 1, with tacrolimus administered on postoperative day 2 or day 3.
The values of area under the plasma concentration time curve for 0 to 12 hours were significantly higher in the 3000 mg/day mycophenolate mofetil suspension group than in the 2000 mg/day mycophenolate mofetil suspension group (P = .024) and in the 3000mg/day mycophenolate mofetil capsule group (P = .013). Significant positive correlations were shown between blood concentration at 8 hours after administration and the plasma concentration time curve for 0 to 12 hours (r2 = 0.96; P < .001) in patients in the suspension group. No patients required mycophenolate mofetil reduction because of leukopenia and diarrhea. Only 1 biopsy-proven acute cellular rejection was recognized in the mycophenolate mofetil suspension group (at 2000 mg/day). There were no significant differences in frequency of opportunistic infections among the 3 groups.
Mycophenolate mofetil suspension is useful as part of immunosuppressive induction therapy after living-donor liver transplant because its concentration increases greater than that of mycophenolate mofetil capsules and because of the low risk of rejection and adverse events.
本研究旨在评估霉酚酸酯混悬液用于活体肝移植受者诱导治疗的安全性、耐受性和药代动力学,与霉酚酸酯胶囊进行比较。
2017 年 7 月至 2019 年 4 月,我们回顾性纳入 20 例成人原发性活体肝移植受者。受者分为 3 组:组 1 接受霉酚酸酯混悬液 3000mg(n=6),组 2 接受霉酚酸酯胶囊 3000mg(n=8),组 3 接受霉酚酸酯混悬液 2000mg(n=6)。术后第 1 天开始给药,术后第 2 天或第 3 天给予他克莫司。
3000mg/天霉酚酸酯混悬液组的 0 至 12 小时血药浓度-时间曲线下面积显著高于 2000mg/天霉酚酸酯混悬液组(P=0.024)和 3000mg/天霉酚酸酯胶囊组(P=0.013)。在混悬液组患者中,给药后 8 小时的血药浓度与 0 至 12 小时的血药浓度-时间曲线下面积呈显著正相关(r2=0.96;P<0.001)。无患者因白细胞减少和腹泻而需要减少霉酚酸酯剂量。仅在霉酚酸酯混悬液组(2000mg/天)中发现 1 例经活检证实的急性细胞性排斥反应。3 组间机会性感染的发生率无显著差异。
霉酚酸酯混悬液可作为活体肝移植受者免疫抑制诱导治疗的一种方法,因为其浓度增加大于霉酚酸酯胶囊,且排斥反应和不良事件风险较低。