Clinical Drug Investigation

, Volume 39, Issue 12, pp 1175–1184 | Cite as

Investigation of the Association Between Total and Free Plasma and Saliva Mycophenolic Acid Concentrations Following Administration of Enteric-Coated Mycophenolate Sodium in Adult Kidney Transplant Recipients

  • Emily BrooksEmail author
  • Susan E. Tett
  • Nicole M. Isbel
  • Brett McWhinney
  • Christine E. Staatz
Original Research Article


Background and Objectives

Mycophenolic acid (MPA) is commonly used following renal transplant. Saliva MPA concentrations may reflect the pharmacologically active form of MPA in plasma. Therapeutic drug monitoring using saliva is convenient and non-invasive. This study examined the correlation between total and free plasma and saliva MPA concentrations following enteric-coated mycophenolate sodium (EC-MS) administration in renal transplant recipients.


Total and free plasma and saliva MPA concentrations were measured simultaneously in 20 adult renal transplant recipients 1–2 months’ post-transplant. Thirteen samples were taken pre-dose and at specified time points up until 12 h post-dose.


When considering all time points, correlation between total plasma and saliva MPA was r2 = 0.51 and between free plasma and saliva MPA concentrations r2 = 0.41. The correlation between total plasma MPA area under the concentration–time curve (AUC) or free plasma AUC and saliva MPA AUC was r2 = 0.25 and r2 = 0.13, respectively. The correlation between total plasma MPA AUC and total plasma MPA trough (C0) concentrations was r2 = 0.51, and between total plasma MPA AUC and saliva MPA trough concentrations, r2 = 0.03.


Measurement of MPA concentration in saliva cannot currently replace plasma measurement for therapeutic drug monitoring of MPA following EC-MS administration. Additional studies are required to examine the relationship between MPA saliva concentrations and patient outcomes.



The authors would like to thank the Princess Alexandra Hospital Department of Nephrology medical and nursing staff for their assistance with the study, the patients for their involvement in the study and the reviewers for their helpful comments.

Author contributions

Emily Brooks performed a literature review, designed the study, collected and analysed the data and wrote the manuscript first draft. Susan Tett assisted in literature review, study design and manuscript review. Nicole Isbel assisted in study design, patient recruitment, data collection and manuscript review. Brett McWhinney analysed the samples and assisted with manuscript review. Christine Staatz assisted in literature review, data analysis, study design and manuscript review.

Compliance and Ethical Standards


No sources of funding were used to assist with the preparation of this review. Dr. Brooks was a student; Drs. Tett, Staatz and Isbel receive salaries from university/hospital sources.

Conflict of interest

Dr. Emily Brooks: none to declare. Associate Prof. Christine Staatz: none to declare. Prof. Susan Tett: none to declare. Associate Prof. Nicole Isbel: none to declare. Mr Brett McWhinney: none to declare.

Ethics approval

All procedures in this study were in accordance with the 1964 Helsinki Declaration (and its amendments). The University of Queensland and Princess Alexandra Hospital Ethics Committees approved the study (Approval numbers: 2013000718, HREC/12/QPAH/538).

Informed consent

All patients provided informed written consent.


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.School of MedicineThe University of QueenslandBrisbaneAustralia
  2. 2.School of PharmacyThe University of QueenslandBrisbaneAustralia
  3. 3.Department of NephrologyThe Princess Alexandra HospitalBrisbaneAustralia
  4. 4.Pathology QueenslandRoyal Brisbane and Women’s HospitalBrisbaneAustralia

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