Projects
Lab Projects (2)
Patient collected microsamples for home-based therapeutic drug monitoring
Immunosuppression is a major modifiable factor that can be targeted for improved transplant outcomes. However, clinical practice is limited in balancing the prevention of immune-mediated graft damage with the development of adverse side effects. The application of enhanced TDM strategies, including home-based sample collection to repeatedly measure drug concentration, is necessary to facilitate precision dosing after transplantation. Our work has established analytical assays to obtain drug concentrations from dried samples and added mobile technology to guide the patient through the process. Without new tools to increase the feasibility of enhanced TDM, improving immunosuppression management and increasing graft survival will be difficult. Our work continues to optimize the home-based TDM model through the use of improved health technologies and is working to add the analysis of biomarkers that predict drug exposure-response to the information gathered from dried samples.
This work has led to several peer-reviewed publications advancing home-based therapeutic drug monitoring and microsampling approaches in transplant care:
- Validated two microsampling devices for clinical use in home-based monitoring of immunosuppressant drug levels, supporting feasibility in real-world transplant settings. Read more on PubMed.
- Conducted a systematic review evaluating the strengths and limitations of volumetric absorptive microsampling (VAMS) for monitoring tacrolimus and mycophenolic acid. Read more on PubMed.
- Demonstrated successful application of a novel microsampling device for the quantitative analysis of immunosuppressive therapies, laying the groundwork for broader implementation. Read more on PubMed.
Advance understanding of intrapatient variability in immunosuppression exposure
Interpatient variability in tacrolimus exposure is well-known and driven primarily by pharmacogenomics. However, in the last few years, there has been an increased understanding of the important relationship between increased intrapatient variability and poor transplant outcomes (graft loss, rejection, etc). The causes of intrapatient variability are poorly understood and hypothesized to be related to multiple factors such as medication adherence, drug interactions, and pharmacogenomics. We have led several research projects focused on understanding the causes and contribution of these factors on intrapatient implement interventions to improve transplant outcomes. We are working to identify how patient behavior, and biomarkers can be used to help understand the variability we see.
Our work investigating intrapatient tacrolimus variability has resulted in several key publications that explore its underlying causes and clinical consequences:
- We applied a comprehensive mixed-method approach—including systematic review, meta-analysis, and retrospective data analysis—to characterize diurnal variability in tacrolimus exposure among pediatric patients. Read more on PubMed.
- Our findings demonstrated that CYP3A5 genotype significantly influences tacrolimus time in therapeutic range and outcomes in pediatric kidney and heart transplant recipients. Read more on PubMed.
- We offered a multiorgan perspective on intrapatient variability in tacrolimus exposure, consolidating knowledge across solid organ transplant populations. Read more on PubMed.
- Earlier work also identified a clinically relevant drug–drug interaction between cannabidiol and tacrolimus, with implications for therapeutic management in transplant patients. Read more on PubMed.
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