Influence of sex and race on mycophenolic acid pharmacokinetics in stable African American and Caucasian renal transplant recipients.
Influence of sex and race on mycophenolic acid pharmacokinetics in stable African American and Caucasian renal transplant recipients.
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DOI：
10.1007/s40262-014-0213-7
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发表时间：
2015-04
影响因子：
4.5
通讯作者：
Venuto, Rocco C.
中科院分区：
文献类型：
--
作者：
Tornatore, Kathleen M.;Meaney, Calvin J.;Wilding, Gregory E.;Chang, Shirley S.;Gundroo, Aijaz;Cooper, Louise M.;Gray, Vanessa;Shin, Karen;Fetterly, Gerald J.;Prey, Joshua;Clark, Kimberly;Venuto, Rocco C.
在肠溶霉酚钠(ECMPS)和他克莫司免疫抑制期间，没有关于性别和种族对MPA药代动力学和不良反应(AE)的影响的评估。67例稳定的肾移植受者中，22例非裔美国人(AAM)，13名AA女性(AAF)，16名高加索男性(CM)和16名高加索女性(CF)接受ECMPS和他克莫司治疗，研究了MPAG和MPAG在胃肠道AE中的药代动力学。有效的胃肠道AE分级包括腹泻、消化不良、呕吐和完成抑酸治疗。采用包含胃肠道声发射和临床协变量的统计模型确定表观清除量、与体重指数(BMI)归一化的清除量、0-12浓度时间曲线下面积(AUC0-12)和剂量归一化AUC 0-12(AUC*)。男性明显快于女性(Cf：8.70±3.33 L/h和AAf：9.71±3.94 L/h；P=0.014)，且存在种族性别交互作用(P=0.043)。不同性别间的MPA清除率/体质量指数(P=0.033)和AUC值(P=0.033)存在性别差异。MPAAUC0-12>60 mg·h/L者占57%，其中71%的患者表现为胃肠道声发射，女性得分较高。在所有患者中，女性的胃肠道声发射评分是男性的1.4倍(P=0.024)。种族(P=0.044)和性别(P=0.005)差异显著，AAF和CF的MPAG AUC0-12较大。性别和种族差异明显，女性的Mpa清除较慢，MPAG AUC0-12较高，胃肠道AUC0-12较严重。这些发现提示在甲孕酮免疫抑制期间考虑性别和种族。
No evaluation of sex and race influences on MPA pharmacokinetics and adverse effects (AE) during enteric coated mycophenolate sodium (ECMPS) and tacrolimus immunosuppression are available. MPA and MPA glucuronide(MPAG) pharmacokinetics with gastrointestinal AE were investigated in 67 stable renal transplant recipients: 22 African American males(AAM); 13 AA females(AAF); 16 Caucasian males(CM) and 16 Caucasian females(CF) receiving ECMPS and tacrolimus. Validated gastrointestinal AE rating included diarrhea, dyspepsia, vomiting and acid suppressive therapy was completed. Apparent clearance, clearance normalized to body mass index (BMI), area under concentration time curve 0-12 (AUC0-12) and dose normalized AUC 0-12 (AUC*) were determined using a statistical model that incorporated gastrointestinal AE and clinical covariates. Males had more rapid apparent MPA clearance (CM: 13.8 ± 6.27 L/h vs. AAM: 10.2 ± 3.73 L/h) compared to females (CF: 8.70 ± 3.33 L/h and AAF: 9.71 ± 3.94 L/hr; P=0.014) with a race-sex interaction (P=0.043). Sex differences were observed in MPA clearance/BMI (P=0.033) and AUC* (P=0.033). MPA AUC0-12 was greater than 60 mg•h/L in 57% of RTR with 71% of patients demonstrating gastrointestinal AE and a higher score noted in females. In all patients, females exhibited 1.40-fold increased gastrointestinal AE scores compared to males (P=0.024). Race (P=0.044) and sex (P=0.005) differences were evident with greater MPAG AUC0-12 in AAF and CF. Sex and race differences were evident with females having slower MPA clearance, higher MPAG AUC0-12 and more severe gastrointestinal AE. These findings suggest consideration of sex and race during MPA immunosuppression.
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影响因子：
2.1
作者：
Langone A;Doria C;Greenstein S;Narayanan M;Ueda K;Sankari B;Pankewycz O;Shihab F;Chan L
通讯作者：
Chan L
影响因子：
6.1
作者：
Grinyo, Josep M.;Ekberg, Henrik;Brunet, Merce
通讯作者：
Brunet, Merce
影响因子：
2.1
作者：
Bunnapradist, Suphamai;Ambuehl, Patrice M.
通讯作者：
Ambuehl, Patrice M.
影响因子：
158.5
作者：
Ekberg, Henrik;Tedesco-Silva, Helio;Halloran, Philip F.
通讯作者：
Halloran, Philip F.
影响因子：
8.8
作者：
Gaston, R.;Kaplan, B.;Bloom, R. D.
通讯作者：
Bloom, R. D.