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, Chin-Hsin Hsu, Hsuan Yin Wu, Yu Ching Huang, Yu Jen Yang, Chwan-Yau Luo

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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

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Mycophenolic Acid
Tacrolimus
Heart Transplantation
Area Under Curve
Leukopenia
Organ Transplantation
Patient Safety

All Science Journal Classification (ASJC) codes

  • Transplantation

Cite this

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title = "Dose-normalization for exposure to mycophenolic acid and the early clinical outcome in patients taking tacrolimus after heart transplantation",
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.",
author = "Jun-Neng Roan and Chen-Hsi Chou and Chin-Hsin Hsu and Wu, {Hsuan Yin} and Huang, {Yu Ching} and Yang, {Yu Jen} and Chwan-Yau Luo",
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T1 - Dose-normalization for exposure to mycophenolic acid and the early clinical outcome in patients taking tacrolimus after heart transplantation

AU - Roan, Jun-Neng

AU - Chou, Chen-Hsi

AU - Hsu, Chin-Hsin

AU - Wu, Hsuan Yin

AU - Huang, Yu Ching

AU - Yang, Yu Jen

AU - Luo, Chwan-Yau

PY - 2013/3/12

Y1 - 2013/3/12

N2 - 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.

AB - 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.

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U2 - 10.12659/AOT.883812

DO - 10.12659/AOT.883812

M3 - Article

VL - 18

SP - 45

EP - 52

JO - Annals of Transplantation

JF - Annals of Transplantation

SN - 1425-9524

IS - 1

ER -