A Review on Therapeutic Drug Monitoring of Immunosuppressant Drugs

Document Type: Review Article


1 Department of Microbiology, School of Medicine, Islamic Azad University, Mashhad Branch, Mashhad, Iran

2 Zakariya Research Centre, Islamic Azad University, Mashhad Branch, Mashhad, Iran

3 Department of Pharmacodinamy and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

4 Department of Pharmacodinamy and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences,Mashhad, Iran

5 Pharmaceutical Research Centre, Mashhad University of Medical Sciences, Mashhad, Iran

6 Department of Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran


Immunosuppressants require therapeutic drug monitoring because of their narrow therapeutic index and significant inter-individual variability in blood concentrations. This variability can be because of factors like drug-nutrient interactions, drug-disease interactions, renal-insufficiency, inflammation and infection, gender, age, polymorphism and liver mass. Drug monitoring is widely practiced especially for cyclosporine, tacrolimus, sirolimus and mycophenolic acid.
Therapeutic monitoring of immunosuppressive therapy with cyclosporine is a critical requirement because of intra- and inter-patient variability of drug absorption, narrow therapeutic window and drug induced nephrotoxicity.
Mycophenolic acid (MPA)
Some reasons for therapeutic drug monitoring of MPA during post-transplant period include: relationship between MPA pharmacokinetic parameters and clinical outcomes, Inter-patient pharmacokinetic variability for MPA despite fixed MMF doses, alternations of MPA pharmacokinetics during the first months after transplantation, drug- drug interaction and influence of kidney function on MPA pharmacokinetic.
A recent review of the pharmacokinetics of sirolimus suggested a therapeutic range of 5 to 10 pg l-1 in whole blood. However, the only consensus guidelines published on the therapeutic monitoring of sirolimus concluded that there was not enough information available about the clinical use of the drug to make recommendations.
Sudies have shown, in kidney and liver transplant patients, significant associations of low tacrolimus concentrations with rejection and of high concentrations with nephrotoxicity. Although the feasibility of a limited sampling scheme to predict AUC has been demonstrated, as yet, trough, or pre-dose, whole blood concentration monitoring is still the method of choice.


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