Ann Hepatobiliary Pancreat Surg.  2017 Feb;21(1):11-16. 10.14701/ahbps.2017.21.1.11.

Intra-individual variability of mycophenolic acid concentration according to renal function in liver transplant recipients receiving mycophenolate monotherapy

Affiliations
  • 1Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. shwang@amc.seoul.kr

Abstract

BACKGROUNDS/AIMS
Mycophenolate mofetil (MMF) has wide inter- and intra-individual variability of mycophenolic acid (MPA) after liver transplantation (LT). On this study, we aimed to analyse the intra-individual variability of MPA concentration in stable adult LT recipients receiving MMF monotherapy and develop a method to determine the target level in the situation of wide intra-individual variability.
METHODS
This retrospective cross-sectional study included 30 LT recipients. All patients received MMF monotherapy at a dose of 500 mg twice daily for ≥2 years and were divided into two groups based on renal function. MPA concentration-associated values were presented as mean with standard deviation and coefficient of variation (CV).
RESULTS
The normal renal function group (n=15) showed a mean 12-hour MPA concentration of 2.5±0.5 µg/ml (range, 1.8±0.5 to 3.6±0.7 µg/ml) and a mean CV of 20.4±7.7% (range, 8.7% to 39.4%). In the renal dysfunction group (n=15), the 12-hour MPA concentration fluctuated more widely with a mean value of 3.7±0.9 µg/ml (range, 2.8±0.8 to 5.1±1.2 µg/ml) and a mean CV of 24.5±4.9% (range, 17.1% to 37.5%). The 12-hour MPA concentration was significantly higher in the renal dysfunction group, as compared to the normal renal function group (p=0.001); whereas, the CV was not significantly different between the two groups (p=0.093).
CONCLUSIONS
We determined the inter- and intra-individual variability of 12-hour MPA concentration after LT. The results suggested that therapeutic drug monitoring of MPA is necessary due to the inter-individual and intra-individual variability of MMF pharmacokinetics, especially in LT recipients with renal dysfunction.

Keyword

Renal function; Mycophenolate mofetil; Mycophenolic acid; Variability; Liver transplantation

MeSH Terms

Adult
Cross-Sectional Studies
Drug Monitoring
Humans
Liver Transplantation
Liver*
Methods
Mycophenolic Acid*
Pharmacokinetics
Retrospective Studies
Transplant Recipients*
Mycophenolic Acid

Figure

  • Fig. 1 Serial measurement of 12-hour mycophenolic acid (MPA) concentration in liver transplant recipients with normal renal function after administration of mycophenolate mofetil 500 mg twice per day.

  • Fig. 2 Serial measurement of 12-hour mycophenolic acid (MPA) concentration in liver transplant recipients with renal dysfunction after administration of mycophenolate mofetil 500 mg twice per day.

  • Fig. 3 Scatter plot of mean 12-hour mycophenolic acid (MPA) concentration and coefficient of variation (CV) in liver transplant recipients with normal renal function (blank circle) and renal dysfunction (solid triangle) after administration of mycophenolate mofetil 500 mg twice per day.


Cited by  3 articles

Cross-sectional analysis of immunosuppressive regimens focused on everolimus after liver transplantation in a Korean high-volume transplantation center
Sang-Hyun Kang, Shin Hwang, Tae-Yong Ha, Gi-Won Song, Dong-Hwan Jung, Chul-Soo Ahn, Deok-Bog Moon, Ki-Hun Kim, Gil-Chun Park, Young-In Yoon, Yo-Han Park, Hui-Dong Cho, Jae-Hyun Kwon, Yong-Kyu Chung, Jin Uk Choi, Sung-Gyu Lee
Korean J Transplant. 2019;33(4):98-105.    doi: 10.4285/jkstn.2019.33.4.98.

A cross-sectional analysis of long-term immunosuppressive regimens after liver transplantation at Asan Medical Center: Increased preference for mycophenolate mofetil
Shin Hwang, Chul-Soo Ahn, Ki-Hun Kim, Deok-Bog Moon, Tae-Yong Ha, Gi-Won Song, Dong-Hwan Jung, Gil-Chun Park, Sung-Gyu Lee
Ann Hepatobiliary Pancreat Surg. 2018;22(1):19-26.    doi: 10.14701/ahbps.2018.22.1.19.

Pretransplant Hepatic Malignancy Increases Risk of De Novo Malignancy after Liver Transplantation
Gil-Chun Park, Shin Hwang, Chul-Soo Ahn, Ki-Hun Kim, Deok-Bog Moon, Tae-Yong Ha, Gi-Won Song, Dong-Hwan Jung, Young-In Yoon, Hui-Dong Cho, Jae-Hyun Kwon, Yong-Kyu Chung, Sang-Hyun Kang, Jin-Uk Choi, I-Ji Jung, Sung-Gyu Lee
J Korean Med Sci. 2020;35(11):.    doi: 10.3346/jkms.2020.35.e69.


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