泰国肾移植患者中霉酚酸酯仿制药与原研药的药代动力学比较研究。

A Study of the Pharmacokinetic Comparison between the Generic and Original Form of Mycophenolate Mofetil Among Thai Renal Transplant Patients.

作者信息

Larpparisuth Nuttasith, Pinpaiboon Soontorn, Ratchawang Nartsiri, Promraj Ratchawat, Skulratanasak Peenida, Vongwiwatana Attapong, Premasathian Nalinee

机构信息

Division of Nephrology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

出版信息

Transplant Proc. 2019 Oct;51(8):2629-2632. doi: 10.1016/j.transproceed.2019.03.063. Epub 2019 Aug 27.

DOI:10.1016/j.transproceed.2019.03.063

PMID:31471014

Abstract

BACKGROUND

Mycophenolic acid (MPA) is one of the main immunosuppressive regimens used after kidney transplantation (KT). The less expensive, generic form of mycophenolate mofetil (MMF) (Immucept) is recently available in Thailand. Comparisons of the pharmacokinetic profiles between the original and generic forms of MMF among post-KT patients are limited.

METHODS

This prospective cohort study recruited KT patients receiving stable doses of MMF 1000 mg daily along with tacrolimus and steroids. All participants were prescribed CellCept 500 mg every 12 hours for at least 2 weeks before measuring the MPA area under the curve from 0 to 12 hours (AUC). CellCept was switched to Immucept 500 mg every 12 hours for 2 weeks and MPA AUC was remeasured.

RESULTS

Twenty patients with a median follow-up time of 35.4 (11.13-198.83) months were enrolled. Mean MPA AUC of Immucept was higher than CellCept without statistical significance (48.27 ± 2.31 μg⋅hr/mL vs 42.19±15.20 μg⋅hr/mL; P value = .59). No difference was revealed regarding the minimum measured concentration, maximum measured concentration, and time point with maximum concentration between both drugs. While on CellCept, 5 patients (25%) had an MPA AUC < 30.0 μg⋅hr/mL, but 3 patients (15%) had MPA AUC < 30.0 μg⋅hr/mL when receiving Immucept. However, 3 (15%) and 6 (30%) patients had MPA AUC > 60.0 μg⋅hr./mL when treated with CellCept and Immucept, respectively.

CONCLUSION

Generic MMF exhibited a comparable pharmacodynamic profile as the original formulation. MPA AUC was more than 30.0 μg⋅hr/mL among most patients receiving MMF 1000 mg/day.

摘要

背景

霉酚酸（MPA）是肾移植（KT）后使用的主要免疫抑制方案之一。霉酚酸酯（MMF）较便宜的仿制药（Immucept）最近在泰国上市。肾移植术后患者中MMF原研药和仿制药的药代动力学特征比较有限。

方法

这项前瞻性队列研究招募了接受稳定剂量的每日1000 mg MMF以及他克莫司和类固醇的肾移植患者。在测量0至12小时MPA曲线下面积（AUC）之前，所有参与者均每12小时服用500 mg骁悉至少2周。将骁悉换为每12小时500 mg Immucept，持续2周，并重新测量MPA AUC。

结果

纳入了20例患者，中位随访时间为35.4（11.13 - 198.83）个月。Immucept的平均MPA AUC高于骁悉，但无统计学意义（48.27±2.31μg·hr/mL对42.19±15.20μg·hr/mL；P值 = 0.59）。两种药物在最低测量浓度、最高测量浓度和最大浓度时间点方面均无差异。服用骁悉时，5例患者（25%）的MPA AUC < 30.0μg·hr/mL，但接受Immucept时，3例患者（15%）的MPA AUC < 30.0μg·hr/mL。然而，接受骁悉和Immucept治疗时，分别有3例（15%）和6例（30%）患者的MPA AUC > 60.0μg·hr./mL。