Limited Sampling Strategy for the Estimation of Mycophenolic Acid and its Acyl Glucuronide Metabolite Area under the Concentration-Time Curve in Japanese Lung Transplant Recipients

Authors

  • Masaki Tanaka Department of Pharmaceutical Sciences, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan.
  • Masafumi Kikuchi Department of Pharmaceutical Sciences, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan. Faculty of Pharmaceutical Sciences, Tohoku University, 6-3 Aramaki-Aza-Aoba, Aoba-ku, Sendai, Japan.
  • Shinya Takasaki Department of Pharmaceutical Sciences, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan.
  • Tensei Hirasawa Faculty of Pharmaceutical Sciences, Tohoku University, 6-3 Aramaki-Aza-Aoba, Aoba-ku, Sendai, Japan.
  • Kensuke Sigeta Faculty of Pharmaceutical Sciences, Tohoku University, 6-3 Aramaki-Aza-Aoba, Aoba-ku, Sendai, Japan.
  • Aoi Noda Department of Pharmaceutical Sciences, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan.
  • Miki Akiba Department of Organ Transplantation Center, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan.
  • Yasushi Matsuda Department of Thoracic Surgery, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan.
  • Hisashi Oishi Department of Thoracic Surgery, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan.
  • Tetsu Sado Department of Thoracic Surgery, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan.
  • Masafumi Noda Department of Thoracic Surgery, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan.
  • Yoshinori Okada Department of Organ Transplantation Center, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan. Department of Thoracic Surgery, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan.
  • Nariyasu Mano Department of Pharmaceutical Sciences, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan. Faculty of Pharmaceutical Sciences, Tohoku University, 6-3 Aramaki-Aza-Aoba, Aoba-ku, Sendai, Japan.
  • Hiroaki Yamaguchi Department of Pharmaceutical Sciences, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan. Faculty of Pharmaceutical Sciences, Tohoku University, 6-3 Aramaki-Aza-Aoba, Aoba-ku, Sendai, Japan. http://orcid.org/0000-0003-3021-6120

DOI:

https://doi.org/10.18433/jpps30505

Abstract

Purpose: The dose of mycophenolate mofetil (MMF) used to prevent rejection after lung transplantation is often adjusted based on the 12-hour area under the concentration-time curve (AUC0-12) of mycophenolic acid (MPA). A limited sampling strategy (LSS) is useful to define the pharmacokinetic (PK) profiles of MPA and mycophenolic acid acyl glucuronide (AcMPAG). Therefore, this study aimed to design a LSS based on multiple linear regression for estimating the AUC0-12 of MPA and AcMPAG at the minimum blood sampling points in Japanese lung transplant patients with concomitant tacrolimus. Methods: Forty-five lung transplantation recipients were enrolled in a PK study of MPA, mycophenolic acid glucuronide (MPAG), and AcMPAG. The plasma MPA, MPAG, and AcMPAG concentrations were determined just before and at 0.5, 1, 2, 4, 8, and 12 hours after dosing. The AUC0-12 of MPA and AcMPAG was calculated using a linear trapezoidal rule from the plasma concentration of each blood sampling time. LSS was used to develop models for estimated AUC in the model group (n = 23) and was evaluated in the validation group (n = 22). Results: The best three time-point equation was 4.04 + 1.64·C1 + 3.08·C4 + 5.17·C8 for MPA, and -0.13 + 3.01·C1 + 3.51·C4 + 5.74·C8 for AcMPAG. The prediction errors (PE) and the absolute prediction errors (APE) were within the clinically acceptable ± 5% and 15% range, respectively (MPA: PE = 2.00%, APE = 11.66%, AcMPAG: PE = 0.98%, APE = 14.69%). The percentage of estimated AUC0-12 within ± 15% of the observed AUC0-12 was 77.27% for MPA and 81.82% for AcMPAG. Conclusion: LSS using three time-point (C1, C4, and C8) provides the most reliable and accurate simultaneous estimation of the AUC0-12 of MPA and AcMPAG in Japanese lung transplant patients.

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Published

2019-08-20

How to Cite

Tanaka, M., Kikuchi, M., Takasaki, S., Hirasawa, T., Sigeta, K., Noda, A., … Yamaguchi, H. (2019). Limited Sampling Strategy for the Estimation of Mycophenolic Acid and its Acyl Glucuronide Metabolite Area under the Concentration-Time Curve in Japanese Lung Transplant Recipients. Journal of Pharmacy & Pharmaceutical Sciences, 22(1), 407–417. https://doi.org/10.18433/jpps30505

Issue

Vol. 22 (2019): Pages 365 - 629

Section

Pharmaceutical Sciences; Original Research Articles

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