DIAGREAT TDM provides the support for MPA individualized treatment
发布日期:
2024-12-12
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Mycophenolic acid (MPA) is an immunosuppressant derived from penicillin bacteria and is mainly used to prevent and treat acute rejection after organ transplantation [1]. It inhibits the proliferation of T and B lymphocytes by blocking the synthesis of purine nucleotides through inhibition of hypoxanthine mononucleotide de hydrogenase (IMPDH) [1]. MPA is often used clinically in combination with drugs such as cyclosporine A or tacrolimus to enhance the immunosuppressive effect. In addition to organ transplantation, mycophenolic acid has been used in the treatment of certain autoimmune diseases such as lupus nephritis and vasculitis [2].



Clinical challenges of mycophenolic acid


Challenges encountered in the clinical application of mycophenolic acid mainly include the need for individualized drug delivery, as the metabolism and response to mycophenolic acid varies significantly from patient to patient, and drug concentration monitoring is required to achieve individualized treatment. In addition, the technology of drug concentration monitoring is itself complex and requires the selection of appropriate monitoring methods, such as the LC-MS/MS method, which is costly in terms of equipment and complicated to operate. Meanwhile, interactions of mycophenolic acid with other drugs may affect its efficacy and safety and need to be carefully managed. These challenges require careful monitoring and adjustment of dosing by healthcare professionals to ensure that mycophenolic acid can be used safely and effectively in transplant patients.


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Significance of mycophenolic acid TDM
1. Individualized administration

The pharmacokinetics and pharmacodynamics of mycophenolic acid differ significantly between patients, and these differences are affected by a variety of factors such as gender, body weight, ethnicity, albumin level, hepatic and renal function, post-transplantation time, and genetic polymorphisms. Studies have shown [3] that when administered at a fixed dose, the trough concentration of mycophenolic acid (C0) can vary up to 10-fold and the AUC0-12 can vary up to 5-fold between patients, while the area under the curve at the time of administration (AUC0-12 ) is significantly correlated with the immunosuppressive efficacy of mycophenolic acid and the toxic side-effects,which shows that there is a large individual variability in the level of mycophenolic acid exposure in vivo. Therefore, individualized administration of mycophenolic acid in combination with therapeutic drug monitoring (TDM) is required in clinical applications.

2.Improvement of clinical efficacy and reduction of adverse reactions

Transplant centers at home and abroad recommend that MPA AUC0-12h be controlled within 30-60 mg.h-1.L-1 , and this therapeutic window range is recommended to be graded as (B, II) in the newly published consensus report on individualized treatment of MPA[3] . Mycophenolic acid blood levels were significantly correlated with immunosuppressive efficacy and toxic side effects. When AUC0-12h <30mg.h-1.L-1 , there is an increased probability of acute rejection, while AUC0-12h >60mg.h-1.L-1 is susceptible to adverse reactions such as leukopenia, anemia, and increased risk of infection[5] . Therefore, blood concentration testing of MPA is of great significance to improve its clinical efficacy and reduce the incidence of adverse reactions.

3. Reduce the dosage of corticosteroids

Through mycophenolic acid therapeutic drug monitoring (TDM), the dose of mycophenolate mofetil (MMF) can be rationally adjusted, so that the MPA-AUC0-12h reaches 30~60 mg.h-1.L-1[3]. By monitoring the blood concentration of MPA, doctors can adjust the treatment program in time in order to achieve optimal therapeutic efficacy and minimize the side effects, especially in the transplantation stabilization period using a low-dose or withdrawal of calcineurin phosphatase inhibitors (e.g., cyclosporine A and tacrolimus) or corticosteroids in the regimen, by monitoring MPA thereby safely and effectively reducing the dosage of corticosteroids.

4. Prediction of hematologic adverse effects

Studies have shown significant associations between free mycophenolic acid (fMPA) concentrations and hematologic adverse effects, including leukopenia and thrombocytopenia, with a negative correlation between the free MPA fraction and leukocyte counts [4]. Albumin levels were significantly positively correlated with MPA exposure, whereas leukocyte levels were significantly negatively correlated with it. This implies that changes in albumin levels can be used as a reference factor for adjusting MPA dosage to minimize the incidence of hematologic adverse reactions. The cut-off values of MPA AUC for predicting under-exposure to MPA and leukopenia were 126.3 mg.h-1.L-1, respectively. This suggests that by monitoring the AUC of MPA, it is possible to predict the risk of hematologic adverse reactions and to adjust the therapeutic regimen accordingly [5] .

DIAGREAT TDM provides the support for MPA individualized treatment


In summary, mycophenolic acid drug concentration testing is clinically important to ensure the safe and effective use of mycophenolic acids in transplant patients, optimize treatment regimens, reduce adverse reactions, and individualize treatment. The TDM solution for mycophenolic acid drugs derived from DANDA company provides strong clinical support with its high sensitivity and accuracy.


DIAGREAT TDM provides the support for MPA individualized treatment



DIAGREAT TDM provides the support for MPA individualized treatment


DIAGREAT TDM provides the support for MPA individualized treatment

Reference:

1. Siebert A, Prejs M, Cholewinski G, Dzierzbicka K. New Analogues of Mycophenolic Acid. Mini Rev Med Chem. 2017;17(9):734-745. doi: 10.2174/1389557516666161129160001. PMID: 27903231.
2. Shaw LM, Nowak I. Mycophenolic acid: measurement and relationship to pharmacologic effects. Ther Drug Monit. 1995 Dec;17(6):685-9. doi: 10.1097/00007691-199512000-00024. PMID: 8588242.
3. 张相林.治疗药物监测临床应用手册 [M]. 北京: 人民卫生出版社, 2020.
4. Tönshoff B. Immunosuppressants in Organ Transplantation. Handb Exp Pharmacol. 2020;261:441-469. doi: 10.1007/164_2019_331. PMID: 31820175.
5. Bolin P Jr, Gohh R, Kandaswamy R, Shihab FS, Wiland A, Akhlaghi F, Melancon K. Mycophenolic acid in kidney transplant patients with diabetes mellitus: does the formulation matter? Transplant Rev (Orlando). 2011 Jul;25(3):117-23. doi: 10.1016/j.trre.2010.12.003. Epub 2011 Apr 29. PMID: 21530217.



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