fast, accurate and remote tacrolimus blood level monitoring

At the 2019 meeting of the American Transplant Congress, held this year in Boston, scientists from the Oslo University Hospital, Rikshospitalet presented exciting findings regarding more patient-centered AUC-monitoring of tacrolimus, a cornerstone immunosppressant, using blood microsampling systems driven by Mitra^® devices and Volumetric Absorptive Microsampling (VAMS™) technology. Researcher and PhD student Marte Theie Gustavsen was on hand to give the presentation and made time to answer a few questions.

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. Thus, more precise, more convenient methods of tacrolimus monitoring are in demand. It is important that monitoring be accurate; thus, patients should be incentivized to comply with monitoring, as well as treatment, as much as possible.

“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.”

Research and Results

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

What Does It Mean for Better 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.” Thus, the study showcases the convenience and user-friendliness of microsampling, both at home and in the lab, and why it’s so powerful for keeping transplant patients healthy and safe.

Goal: The Best Possible Treatment for Transplant Patients

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

“The use of microsampling in an at-home setting 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 affect patient’s quality of life to the better. After all, our goal is to give the best possible treatment to our patients.”

Thinking Long-term

“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 wait several hours to meet the physician. This is time-consuming, and some patients have to travel long distances. Remote patient monitoring through microsampling would reduce patient burden and make the blood sample procedure more patient-friendly. A fixed sample volume from a single finger-prick can be obtained in an at home-setting. Compared to other home-based methods, blood volume absorbed on the Mitra tip is not dependent on hematocrit level, which is important, as the hematocrit level change with time after transplantation.”

Thus, blood microsampling via Mitra devices and VAMS 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. Clearly, scientists and healthcare decisionmakers can see it, too.