Dose-normalization for exposure to mycophenolic acid and the early clinical outcome in patients taking tacrolimus after heart transplantation

Jun Neng Roan, Chen Hsi Chou, Chih Hsin Hsu, Hsuan Yin Wu, Yu Ching Huang, Yu Jen Yang, Chwan Yau Luo

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

The early phase of MPA exposure has rarely been investigated after solid organ transplantation, especially in heart transplantation patients. We evaluated the association between exposure to mycophenolic acid (MPA), a main metabolite of mycophenolate mofetil (MMF), and clinical events within 3 months after heart transplantation. Trough (C0) and area under the curve (AUC)0 levels of MPA and its metabolite, mycophenolic acid glucuronide (MPAG), were determined using high-performance liquid chromatography. Corresponding clinical endpoints included acute rejection or MMF-related adverse events (gastrointestinal symptoms, leucopenia, and anemia). AUC measurements (n=77) were collected from 21 patients. Dose-normalized C0 and AUC0-1 levels were used to evaluate the association between MPA or MPAG exposure and MMF-related adverse events. No acute rejection or mortality occurred during the follow-up period. Twelve patients (57%) developed 13 MMF-related adverse events. The MMF dose was tapered from 2.50 g/day on D1 to 1.55±0.54 g/day on D90. Significantly higher levels of dose-normalized MPA C0 and AUC h were associated with the events than with the absence of the events (C: 1.04±0.42 vs. 0.84±0.85 μg/mL/g [p=0.047]; AUC0-: 20.37±3.21 vs. 14.97±1.13 μg × h/mL/g; [p=0.038]). Dose-normalized MPA exposure may protect against MMF toxicity in the early stage after heart transplantation. The MMF dose can be decreased to near 1.5 g/day 3 months post-transplantation without jeopardizing patient safety; a well-planned, tapered MMF regimen should also be considered.

Original languageEnglish
Pages (from-to)45-52
Number of pages8
JournalAnnals of Transplantation
Volume18
Issue number1
DOIs
Publication statusPublished - 2013 Mar 12

All Science Journal Classification (ASJC) codes

  • Transplantation

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