腹腔镜袖状胃切除术后免疫抑制剂的药代动力学和药物遗传学分析。

Pharmacokinetic and pharmacogenetic analysis of immunosuppressive agents after laparoscopic sleeve gastrectomy.

作者信息

Diwan Tayyab S, Lichvar Alicia B, Leino Abbie D, Vinks Alexander A, Christians Uwe, Shields Adele R, Cardi Michael A, Fukuda Tsuyoshi, Mizuno Tomoyuki, Kaiser Tiffany, Woodle E Steve, Alloway Rita R

机构信息

Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

出版信息

Clin Transplant. 2017 Jun;31(6). doi: 10.1111/ctr.12975. Epub 2017 May 2.

DOI:10.1111/ctr.12975

PMID:28342282

Abstract

BACKGROUND

Severe obesity has been shown to limit access to renal transplantation in patients with end-stage renal disease (ESRD). Laparoscopic sleeve gastrectomy (LSG) has been performed in the ESRD population to assist in achieving waitlist and transplant eligibility. Little is known about how LSG impacts the bioequivalence of tacrolimus products and immunosuppression pharmacokinetics.

METHODS

This was a prospective, open-label, single-dose, crossover, two-period pharmacokinetic (PK) study. The purpose of this study was to assess single-dose PK of immediate-release tacrolimus (IR-TAC), extended-release tacrolimus (ER-TAC), and mycophenolic acid (MPA) in adult ESRD patients post-LSG.

RESULTS

Twenty-three subjects were included in the 24-hour PK assessments. The ratio of geometric means between ER-TAC and IR-TAC was 103.5% (90% CI; 89.6%-119.6%) for AUC and 92.5% (90% CI; 80.4%-106.4%) for C . PK parameters were similar between ER-TAC and IR-TAC, except for C (P=.004) and C (P=.04). MPA AUC was similar when given with either ER-TAC or IR-TAC (P=.32). Patients expressing CYP3A51 genotypes had lower tacrolimus AUC values vs those with CYP3A53/*3 (IR-TACP<.001; ER-TACP=.008). Genotype did not impact MPA PK.

CONCLUSION

Dose modification of immunosuppressants post-LSG may not be necessary aside from standard therapeutic drug monitoring.

摘要

背景

严重肥胖已被证明会限制终末期肾病（ESRD）患者获得肾移植的机会。腹腔镜袖状胃切除术（LSG）已在ESRD患者中实施，以帮助其获得等待名单资格并符合移植条件。关于LSG如何影响他克莫司产品的生物等效性和免疫抑制药代动力学，人们知之甚少。

方法

这是一项前瞻性、开放标签、单剂量、交叉、两期药代动力学（PK）研究。本研究的目的是评估成年ESRD患者接受LSG术后立即释放他克莫司（IR-TAC）、缓释他克莫司（ER-TAC）和霉酚酸（MPA）的单剂量PK。

结果

24小时PK评估纳入了23名受试者。ER-TAC与IR-TAC的几何平均比值，AUC为103.5%（90%CI；89.6%-119.6%），C为92.5%（90%CI；80.4%-106.4%）。除C（P=0.004）和C（P=0.04）外，ER-TAC和IR-TAC的PK参数相似。与ER-TAC或IR-TAC联用时，MPA的AUC相似（P=0.32）。表达CYP3A51基因型的患者他克莫司AUC值低于CYP3A53/*3基因型患者（IR-TAC P<0.001；ER-TAC P=0.008）。基因型不影响MPA的PK。