fast, accurate and remote tacrolimus blood level monitoring

At the 2019 meeting of the American Transplant Congress in Boston, scientists from the Oslo University Hospital, Rikshospitalet presented exciting findings regarding more patient-centered AUC-monitoring of tacrolimus, a cornerstone immunosuppressant, using remote blood microsampling approaches enabled by Mitra^® devices based on VAMS^® technology.

Researcher and PhD student Marte Theie Gustavsen (aka: Marte Theie Mol) gave a presentation on using Mitra with volumetric absorptive microsampling for therapeutic drug monitoring, or TDM, of patients who have had kidney transplants. After her presentation, she made time to answer a few questions about using remote microsampling for TDM.

Tacrolimus Monitoring: Why It Matters

In the administration of tacrolimus, an immunosuppressant drug given to kidney transplant patients to help them avoid rejection, precise tacrolimus levels are required in the bloodstream. However, it can be challenging to get precise drug levels from blood samples.

Thus, more precise, more convenient methods of tacrolimus monitoring are in demand. It is important that monitoring is accurate, yet patients don't always comply with monitoring or properly adhere to their treatment, which can lead to negative effects of tacrolimus and other health problems.

“Too high exposure of tacrolimus increases the risk of hypertension, post-transplant diabetes mellitus, and neurotoxicity, while acute rejection episodes and development of donor specific antibodies are associated with too low exposure.”

Tacrolimus Monitoring Research and Results

During their research, the Oslo team performed a 12-hour pharmacokinetic investigational study in 27 renal transplant patients. Blood sampling occurred 13 times during the dose interval, using both standard venipuncture blood collection and microsampling (finger-stick blood collection).

The Mitra microsample assay fulfilled the criteria on bioanalytical method validation, producing results comparable to those obtained through standard venipuncture. The team published its full results for further study. Their influence on tacrolimus monitoring is likely to be substantial.

Microsampling for Better Tacrolimus Monitoring

“Therapeutic drug monitoring of Tacrolimus is usually performed using pre-dose concentrations, mostly due to practical reasons,” says Gustavsen. “However, a pre-dose concentration gives little information about systemic exposure, and area under the concentration versus time curve - AUC - has been suggested to be the best pharmacokinetic marker for therapeutic drug monitoring of tacrolimus.” So how do we measure it?

“With the use of population pharmacokinetic models and limited sampling strategies, three optimally timed sampling points can give accurate predictions of AUC,” Gustavsen says. “By using microsampling, a sufficient number of blood samples within a dose interval, without any restriction in sampling time, can be obtained in an at-home setting by patients themselves. This will enable and simplify dose adjustments of tacrolimus based on AUC, which in turn hopefully will improve clinical outcome.”

The Oslo study showcases the convenience and user-friendliness of remote microsampling devices, both at home and in the lab, and why the remote approach to therapeutic drug monitoring is effective in keeping transplant patients healthy and safe at home, yet on the right track for post-transplant recovery and maintenance.

Goal: Best Possible Treatment for Transplant Patients

The Oslo team found that the use of remote blood microsampling devices made the study run much more smoothly than anticipated. “After systematic patient training and guidance on the microsample procedure and handling, the patients collected several microsamples by themselves in a home setting. None of the patients reported any sampling difficulties, which indicates that the clinical application of Mitra microsampling is possible,” says Gustavsen.

“The use of microsampling in at-home settings by patients themselves would simplify and improve the follow-up of renal transplant patients,” Gustavsen says. “This is a more patient-friendly way to obtain blood samples and will hopefully impact patients' quality of life for the better. After all, our goal is to give the best possible treatment to our patients.”

Thinking Long-term: Remote Patient Monitoring

“Renal transplant patients need lifelong follow-up with routinely blood sampling performed every month for the rest of their lives,” says Gustavsen. “Patients then have to come to the hospital in the early morning, draw a large blood volume, before waiting several hours to meet the physician. This is time-consuming, and some patients have to travel long distances.

Remote patient monitoring through remote microsampling paired with telehealth technologies would reduce patient burden and make the blood sample collection procedure more patient-friendly. A fixed sample volume from a single finger-prick can be obtained in a home setting. Compared to other home-based methods, blood volume absorbed on the VAMS tip ot a Mitra device is not dependent on hematocrit level, which is important, as the hematocrit level changes with time after transplantation.”

Thus, blood microsampling using Mitra devices with volumetric absorptive microsampling technology creates better long-term conditions for transplant patients. Meanwhile, it opens new opportunities and pathways of care across the landscape of immunosuppressant monitoring and patient-centered medicine.

“Patients were very motivated to participate in our study and saw the benefit this would have for them in the future,” says Gustavsen.

To learn more about using remote microsampling for your TDM programs, visit our page dedicated to: 

Image Credits: The Oslo University Hospital, Rikshospitalet; Trajan, Neoteryx