therapeutic drug monitoring of immunosuppressants: an overview
When administering immunosuppressants, clinicians need to individualize a patient’s drug therapy. The goal is to attain an optimal balance between therapeutic efficacy and the probability of adverse effects. Patients present varying pharmacodynamics and pharmacokinetics, so achieving this goal can be challenging.
Early on, clinicians used analytical techniques to measure drug concentrations in biological fluids during drug treatment. However, the emergence of therapeutic drug monitoring (TDM) offered an opportunity to minimize the pharmacokinetic component of variability by managing drug therapy using concentrations in the body instead of dosages.
That’s why TDM is used before administering immunosuppressants. Drug concentrations in immunosuppressants can cause adverse effects on transplant patients.
Supratherapeutic drug concentrations, for example, put the patient at-risk of over-immunosuppression which leads to infection. Subtherapeutic drug concentrations can cause the recipient’s body to reject an allograft. This interindividual variability in drug concentrations creates the need for TDM.
Immunosuppressants Needing TDM
Factors that cause interindividual variability include:
- Drug-nutrient interactions
- Drug-disease interactions
- Liver mass
- Renal insufficiency
Immunosuppressants that need TDM include:
- Cyclosporine – This immunosuppressant is used to prevent graft rejection in organ transplant patients. Cyclosporine has proven to be effective in improving long-term survival of solid-organ transplant patients. TDM of cyclosporine is essential because of:
- Drug-induced nephrotoxicity
- Inter/intra-patient variability of drug absorption
- Narrow therapeutic window
- Mycophenolic Acid (MPA) – MPA is effective at reducing acute organ rejection in heart, kidney, or renal transplant patients. MPA has also been used along with sirolimus and tacrolimus. Additionally, the drug has recently gained popularity as the primary component in long-term immunosuppressant routines.
However, TDM is essential when using MPA on post-transplant patients because of the interaction of drugs and its effect on kidney functions. Researchers should also consider inter-patient pharmacokinetic variability for MPA and the relationship between MPA and pharmacokinetic parameters.
- Tacrolimus – Tacrolimus has a narrow therapeutic window. This drug exhibits large intra-/inter-individual inconsistency during pharmacokinetics assessment in liver and kidney transplant patients.
The patients display significant associations between high concentrations with nephrotoxicity and low tacrolimus concentrations with rejection. That makes routine TDM of whole blood concentration critical.
Why Microsampling is Important in Therapeutic Drug Monitoring
Just a few decades ago, conventional techniques such as venous blood sampling were used to obtain plasma or serum samples for TDM. With the invention of dried blood sampling, clinicians can enjoy a simple and convenient sampling method.
DBS (dried blood spot) sampling involves taking blood samples with a small finger prick using an automatic lancet. With the right setup, the right equipment, and adequate training, patients can do this themselves.
Mitra microsampling devices are the most convenient system for self-administered blood sampling for immunosuppressant monitoring.