Department of Pharmacy, Faculty of Medicine, University of Nis, Bulevar dr Zorana Djindjica 81, Nis, 18000, Serbia.
Clinic of Nephrology, Clinical Centre Nis, Nis, Serbia.
Int J Clin Pharm. 2019 Jun;41(3):776-784. doi: 10.1007/s11096-019-00837-z. Epub 2019 Apr 26.
Background Mycophenolic acid is widely used immunosuppressive drug, associated with adverse effects which increase patient morbidity and decrease medication adherence. Objective To evaluate the adverse effects in renal transplant recipients under mycophenolate treatment with respect to gender. Setting University Clinical Centre of Nis, Clinic of Nephrology, Serbia. Method This research included 96 renal transplant recipients, who received immunosuppressive regimen, based on tacrolimus or cyclosporin A, prednisone and mycophenolic acid. The high-performance liquid chromatography method combined with protein precipitation was used for the analysis of mycophelate concentration in human plasma. Drug concentration and dose-adjusted concentration were determined with respect to the patients' gender. An adverse effect scoring system developed by nephrologists within the University of Buffalo Nephrology/Transplant Program was used to monitor adverse effects of therapy. Main outcome measure Individual and scores of adverse effects in relation to the dosing regimen and gender. Results Results showed statistically lower dose and concentrations in men compared to the women in our investigation group. Also, female patients demonstrated higher mean scores (cumulative and subscores) within the same dosing regimens of mycophenolic acid. The gastrointestinal score was significantly higher in women who received a dose greater than 720 mg compared to men (0.20 ± 0.12 vs 0.12 ± 0.12). Women demonstrated higher individual adverse effects such as diarrhea and skin changes (41.7 vs 17.0; p = 0.038 and 62.5 vs 30.2; p = 0.037, respectively). Conclusions The results of our research showed that recipients' gender may play an important role in pharmacokinetic profile of mycophenolic acid, suggesting that women had higher concentration of mycophenolic acid and more serious side effects.
麦考酚酸是一种广泛应用的免疫抑制剂，与增加患者发病率和降低药物依从性的不良反应有关。
评估在使用吗替麦考酚酯治疗的肾移植受者中，性别对不良反应的影响。
塞尔维亚尼什大学临床中心，肾病科。
这项研究包括 96 名接受免疫抑制方案治疗的肾移植受者，该方案基于他克莫司或环孢素 A、泼尼松和吗替麦考酚酯。采用高效液相色谱法结合蛋白沉淀法检测人血浆中麦考酚酸的浓度。根据患者的性别确定药物浓度和剂量调整后的浓度。采用布法罗大学肾病/移植项目的肾病学家开发的不良反应评分系统监测治疗的不良反应。
与剂量方案和性别相关的个体和不良反应评分。
结果显示，与女性相比，我们研究组中的男性接受的剂量和浓度较低。此外，在相同的吗替麦考酚酯剂量方案下，女性患者的平均评分（累积评分和亚评分）更高。与男性相比，接受剂量大于 720mg 的女性胃肠道评分更高（0.20±0.12 比 0.12±0.12）。女性还表现出更高的个体不良反应，如腹泻和皮肤变化（41.7 比 17.0；p=0.038 和 62.5 比 30.2；p=0.037）。
我们的研究结果表明，受者的性别可能在麦考酚酸的药代动力学特征中起重要作用，表明女性的麦考酚酸浓度更高，且不良反应更严重。
