Logo Annals of Transplantation Logo Annals of Transplantation Logo Annals of Transplantation

01 January 2008

Therapeutic drug monitoring of immunosuppressive drugs – future perspectives

P. Wallemacq

Ann Transplant 2008; 13(1): 29-29 :: ID: 880183


The dramatic improvement recorded during this last decade in the field of transplantation is mainly due both to the appearance of new immunosuppressive drugs (IS)/drug combinations and to a better understanding of the tenuous equilibrium between over- and under- immunosuppression. Current trends in drug association result in a progressive lowering of the IS charge and consequently in a reduction of their blood concentrations. There is no doubt that therapeutic drug monitoring (TDM) played an important role in this progress, because these are critical dose drugs: concentrations related side effects, inter-patient pharmacokinetics variability (bioavailability, metabolism, drug interactions, genetic polymorphism, ...). Analytical methods used to monitor these drugs also experienced some significant evolution with the use of LC-MSMS in clinical practice and with a constant progress in the immunoassays performances (sensitivity, specificity, reproducibility, automation). The area under the time-concentration curve (AUC) is generally considered as the best drug exposure marker, but is not appropriate in clinical practice. Single time points (mainly C0) IS concentrations remain therefore the most frequently used marker. Blood concentrations monitoring provides some helpful information to prevent side effects, drug interactions or non-compliance. Recent studies, however, suggest that the relationship between blood levels and incidence of organ rejection is not clearly established. Optimal treatment management needs therefore some additional approaches. Four personalized approaches are currently under investigation: 1. Optimization of the prediction of IS AUC with population pharmacokinetics, limited sampling strategy or Bayesian estimates, 2. Identification of genetic polymorphisms of metabolism enzymes or transport proteins (e.g. CYP3A5, P-gp, MRP2, etc.) to reach target drug concentration earlier, 3. Determination of IS drug concentration at the site of action (e.g. within target lymphocytes), and finally 4. Identification of pharmacodynamic biomarkers (e.g. intracellular IL2 in CD8+ T-cells, etc) able to better predict IS drug efficacy (and toxicity). This last approach is of particular interest and is expected to significantly progress during the coming years.

Keywords: Transplantation, immunosuppressive drugs, theory of mind

Add Comment 0 Comments

In Press

12 Feb 2024 : Original article  

No Prognostic Impact of Graft-to-Recipient Weight Ratio on Hepatocellular Carcinoma Recurrence Following Li...

Ann Transplant In Press; DOI: 10.12659/AOT.942767  

21 Feb 2024 : Original article  

Use of LCP-Tacrolimus (LCPT) in Kidney Transplantation: A Delphi Consensus Survey of Expert Clinicians

Ann Transplant In Press; DOI: 10.12659/AOT.943498  

Most Viewed Current Articles

05 Apr 2022 : Original article  

Impact of Statins on Hepatocellular Carcinoma Recurrence After Living-Donor Liver Transplantation

DOI :10.12659/AOT.935604

Ann Transplant 2022; 27:e935604

12 Jan 2022 : Original article  

Risk Factors for Developing BK Virus-Associated Nephropathy: A Single-Center Retrospective Cohort Study of ...

DOI :10.12659/AOT.934738

Ann Transplant 2022; 27:e934738

22 Nov 2022 : Original article  

Long-Term Effects of Everolimus-Facilitated Tacrolimus Reduction in Living-Donor Liver Transplant Recipient...

DOI :10.12659/AOT.937988

Ann Transplant 2022; 27:e937988

15 Mar 2022 : Case report  

Combined Liver, Pancreas-Duodenum, and Kidney Transplantation for Patients with Hepatitis B Cirrhosis, Urem...

DOI :10.12659/AOT.935860

Ann Transplant 2022; 27:e935860

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Annals of Transplantation eISSN: 2329-0358
Annals of Transplantation eISSN: 2329-0358