Population Pharmacokinetics of Mycophenolic Acid in Renal Transplant Patients: A Comparison of the Early and Stable Posttransplant Stages
Mycophenolic acid (MPA) is an antimetabolic immunosuppressive drug widely used in solid organ transplantation and autoimmune diseases. Pharmacokinetics (PK) of MPA demonstrates high inter- and intra-variability. The aim of this study was to compare the population PK properties of MPA in adult renal...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-05-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.859351/full |
| _version_ | 1811306240004849664 |
|---|---|
| author | Peile Wang Peile Wang Hongchang Xie Qiwen Zhang Qiwen Zhang Xueke Tian Xueke Tian Yi Feng Zifei Qin Zifei Qin Jing Yang Jing Yang Wenjun Shang Guiwen Feng Xiaojian Zhang Xiaojian Zhang |
| author_facet | Peile Wang Peile Wang Hongchang Xie Qiwen Zhang Qiwen Zhang Xueke Tian Xueke Tian Yi Feng Zifei Qin Zifei Qin Jing Yang Jing Yang Wenjun Shang Guiwen Feng Xiaojian Zhang Xiaojian Zhang |
| author_sort | Peile Wang |
| collection | DOAJ |
| description | Mycophenolic acid (MPA) is an antimetabolic immunosuppressive drug widely used in solid organ transplantation and autoimmune diseases. Pharmacokinetics (PK) of MPA demonstrates high inter- and intra-variability. The aim of this study was to compare the population PK properties of MPA in adult renal transplant patients in the early and stable post-transplant stages and to simulate an optimal dosing regimen for patients at different stages. A total of 51 patients in the early post-transplant period (1 week after surgery) and 48 patients in the stable state (5.5–10 years after surgery) were included in the study. In the two-compartment population PK model, CL/F (23.36 L/h vs. 10.25 L/h) and V/F (78.07 vs. 16.24 L) were significantly different between the two stages. The dose-adjusted area under the concentration time curve (AUCss,12h/dose) for patients in the early stage were significantly lower than those for patients in the stable state (40.83 ± 22.26 mg h/L vs. 77.86 ± 21.34 mg h/L; p < 0.001). According to Monte Carlo simulations, patients with 1.0–1.5 g of mycophenolate mofetil twice daily in the early phase and 0.50–0.75 g twice daily in the stable phase had a high probability of achieving an AUCss,12h of 30–60 mg h/L. In addition, limited sampling strategies showed that two 4-point models (C0-C1-C2-C4 and C1-C2-C3-C6) performed well in predicting MPA exposure by both Bayesian estimate and regression equation and could be applied in clinical practice to assist therapeutic drug monitoring of MPA. |
| first_indexed | 2024-04-13T08:40:53Z |
| format | Article |
| id | doaj.art-2f9f7539e3b744859be8e5270d788dcc |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-13T08:40:53Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-2f9f7539e3b744859be8e5270d788dcc2022-12-22T02:53:54ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-05-011310.3389/fphar.2022.859351859351Population Pharmacokinetics of Mycophenolic Acid in Renal Transplant Patients: A Comparison of the Early and Stable Posttransplant StagesPeile Wang0Peile Wang1Hongchang Xie2Qiwen Zhang3Qiwen Zhang4Xueke Tian5Xueke Tian6Yi Feng7Zifei Qin8Zifei Qin9Jing Yang10Jing Yang11Wenjun Shang12Guiwen Feng13Xiaojian Zhang14Xiaojian Zhang15Department of Pharmacy, First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, ChinaDepartment of Kidney Transplantation, First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Pharmacy, First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, ChinaDepartment of Pharmacy, First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, ChinaDepartment of Kidney Transplantation, First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Pharmacy, First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, ChinaDepartment of Pharmacy, First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, ChinaDepartment of Kidney Transplantation, First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Kidney Transplantation, First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Pharmacy, First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, ChinaMycophenolic acid (MPA) is an antimetabolic immunosuppressive drug widely used in solid organ transplantation and autoimmune diseases. Pharmacokinetics (PK) of MPA demonstrates high inter- and intra-variability. The aim of this study was to compare the population PK properties of MPA in adult renal transplant patients in the early and stable post-transplant stages and to simulate an optimal dosing regimen for patients at different stages. A total of 51 patients in the early post-transplant period (1 week after surgery) and 48 patients in the stable state (5.5–10 years after surgery) were included in the study. In the two-compartment population PK model, CL/F (23.36 L/h vs. 10.25 L/h) and V/F (78.07 vs. 16.24 L) were significantly different between the two stages. The dose-adjusted area under the concentration time curve (AUCss,12h/dose) for patients in the early stage were significantly lower than those for patients in the stable state (40.83 ± 22.26 mg h/L vs. 77.86 ± 21.34 mg h/L; p < 0.001). According to Monte Carlo simulations, patients with 1.0–1.5 g of mycophenolate mofetil twice daily in the early phase and 0.50–0.75 g twice daily in the stable phase had a high probability of achieving an AUCss,12h of 30–60 mg h/L. In addition, limited sampling strategies showed that two 4-point models (C0-C1-C2-C4 and C1-C2-C3-C6) performed well in predicting MPA exposure by both Bayesian estimate and regression equation and could be applied in clinical practice to assist therapeutic drug monitoring of MPA.https://www.frontiersin.org/articles/10.3389/fphar.2022.859351/fullmycophenolic acidpopulation pharmacokineticspost-transplant periodsAUCrenal transplantation |
| spellingShingle | Peile Wang Peile Wang Hongchang Xie Qiwen Zhang Qiwen Zhang Xueke Tian Xueke Tian Yi Feng Zifei Qin Zifei Qin Jing Yang Jing Yang Wenjun Shang Guiwen Feng Xiaojian Zhang Xiaojian Zhang Population Pharmacokinetics of Mycophenolic Acid in Renal Transplant Patients: A Comparison of the Early and Stable Posttransplant Stages Frontiers in Pharmacology mycophenolic acid population pharmacokinetics post-transplant periods AUC renal transplantation |
| title | Population Pharmacokinetics of Mycophenolic Acid in Renal Transplant Patients: A Comparison of the Early and Stable Posttransplant Stages |
| title_full | Population Pharmacokinetics of Mycophenolic Acid in Renal Transplant Patients: A Comparison of the Early and Stable Posttransplant Stages |
| title_fullStr | Population Pharmacokinetics of Mycophenolic Acid in Renal Transplant Patients: A Comparison of the Early and Stable Posttransplant Stages |
| title_full_unstemmed | Population Pharmacokinetics of Mycophenolic Acid in Renal Transplant Patients: A Comparison of the Early and Stable Posttransplant Stages |
| title_short | Population Pharmacokinetics of Mycophenolic Acid in Renal Transplant Patients: A Comparison of the Early and Stable Posttransplant Stages |
| title_sort | population pharmacokinetics of mycophenolic acid in renal transplant patients a comparison of the early and stable posttransplant stages |
| topic | mycophenolic acid population pharmacokinetics post-transplant periods AUC renal transplantation |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.859351/full |
| work_keys_str_mv | AT peilewang populationpharmacokineticsofmycophenolicacidinrenaltransplantpatientsacomparisonoftheearlyandstableposttransplantstages AT peilewang populationpharmacokineticsofmycophenolicacidinrenaltransplantpatientsacomparisonoftheearlyandstableposttransplantstages AT hongchangxie populationpharmacokineticsofmycophenolicacidinrenaltransplantpatientsacomparisonoftheearlyandstableposttransplantstages AT qiwenzhang populationpharmacokineticsofmycophenolicacidinrenaltransplantpatientsacomparisonoftheearlyandstableposttransplantstages AT qiwenzhang populationpharmacokineticsofmycophenolicacidinrenaltransplantpatientsacomparisonoftheearlyandstableposttransplantstages AT xueketian populationpharmacokineticsofmycophenolicacidinrenaltransplantpatientsacomparisonoftheearlyandstableposttransplantstages AT xueketian populationpharmacokineticsofmycophenolicacidinrenaltransplantpatientsacomparisonoftheearlyandstableposttransplantstages AT yifeng populationpharmacokineticsofmycophenolicacidinrenaltransplantpatientsacomparisonoftheearlyandstableposttransplantstages AT zifeiqin populationpharmacokineticsofmycophenolicacidinrenaltransplantpatientsacomparisonoftheearlyandstableposttransplantstages AT zifeiqin populationpharmacokineticsofmycophenolicacidinrenaltransplantpatientsacomparisonoftheearlyandstableposttransplantstages AT jingyang populationpharmacokineticsofmycophenolicacidinrenaltransplantpatientsacomparisonoftheearlyandstableposttransplantstages AT jingyang populationpharmacokineticsofmycophenolicacidinrenaltransplantpatientsacomparisonoftheearlyandstableposttransplantstages AT wenjunshang populationpharmacokineticsofmycophenolicacidinrenaltransplantpatientsacomparisonoftheearlyandstableposttransplantstages AT guiwenfeng populationpharmacokineticsofmycophenolicacidinrenaltransplantpatientsacomparisonoftheearlyandstableposttransplantstages AT xiaojianzhang populationpharmacokineticsofmycophenolicacidinrenaltransplantpatientsacomparisonoftheearlyandstableposttransplantstages AT xiaojianzhang populationpharmacokineticsofmycophenolicacidinrenaltransplantpatientsacomparisonoftheearlyandstableposttransplantstages |