Clinical validation of two volumetric absorptive microsampling devices to support home-based therapeutic drug monitoring of immunosuppression.

Aims: Dried blood volumetric absorptive microsamples (VAMS) may facilitate home-based sampling to enhance therapeutic drug monitoring after transplantation. This study aimed to clinically validate a liquid chromatography-tandem mass spectrometry assay using 2 VAMS devices with different sampling locations (Tasso-M20 for the upper arm and Mitra for the finger). Patient preferences were also evaluated.

Electronic health record-enabled routine assessment of medication adherence after solid organ transplantation: the time is now.

Medication nonadherence after solid organ transplantation is recognized as an important impediment to long-term graft survival. Yet, assessment of adherence is often not part of routine care. In this Personal Viewpoint, we call for the transplant community to consider implementing a systematic process to screen and assess medication adherence.

Bioanalysis of six antibiotics from volumetric microsamples: a new tool for precision dosing in critically ill children.

Volumetric absorptive microsamples (VAMS) can support pharmacokinetic / pharmacodynamic studies. We present the bioanalytical method development for the simultaneous quantification of ampicillin, cefepime, ceftriaxone, meropenem, piperacillin, tazobactam, and vancomycin from VAMS. Optimal extraction, chromatographic, and mass spectrometry conditions were identified.

A Comprehensive Mixed-Method Approach to Characterize the Source of Diurnal Tacrolimus Exposure Variability in Children: Systematic Review, Meta-analysis, and Application to an Existing Data Set.

Tacrolimus is widely reported to display diurnal variation in pharmacokinetic parameters with twice-daily dosing. However, the contribution of chronopharmacokinetics versus food intake is unclear, with even less evidence in the pediatric population. The objectives of this study were to summarize the existing literature by meta-analysis and evaluate the impact of food composition on 24-hour pharmacokinetics in pediatric kidney transplant recipients.

Volumetric Absorptive Microsampling to Enhance the Therapeutic Drug Monitoring of Tacrolimus and Mycophenolic Acid: A Systematic Review and Critical Assessment.

Background: Volumetric absorptive microsampling (VAMS) is an emerging technique that may support multisample collection to enhance therapeutic drug monitoring in solid organ transplantation. This review aimed to assess whether tacrolimus and mycophenolic acid can be reliably assayed using VAMS and to identify knowledge gaps by providing granularity to existing analytical methods and clinical applications.

Methods: A systematic literature search was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Application of a new volumetric microsampling device for quantitative bioanalysis of immunosuppression.

Volumetric absorptive microsampling may reduce the blood collection burden associated with therapeutic drug monitoring of immunosuppression to prevent organ transplant rejection. This work describes the development of a laboratory and analytical technique for quantifying tacrolimus and mycophenolic acid (MPA) from the Tasso-M20™ in human whole blood using bead-based impact-assisted extraction. The sampled blood volume was accurate with estimated volumes within <2% of the expected 20 μl.

Evaluation of the Relationship between Medication Adherence and Tacrolimus Coefficient of Variation.

High tacrolimus intrapatient variability is associated with poor outcomes following transplantation. A commonly hypothesized cause of this variability is medication non-adherence, but this has not been conclusively demonstrated. The purpose of this study was to evaluate the relationship between medication adherence and tacrolimus intrapatient variability.

Impact of CYP3A5 phenotype on tacrolimus time in therapeutic range and clinical outcomes in pediatric renal and heart transplant recipients.

Study Objective: This study investigated the effect of CYP3A5 phenotype on time in therapeutic range (TTR) of tacrolimus post-transplant in pediatric patients.

Design And Data Source: This retrospective study assessed medical records of pediatric kidney and heart recipients with available CYP3A5 genotype for tacrolimus dosing, troughs, and the clinical events (biopsy-proven acute rejection [BPAR] and de novo donor-specific antibodies [dnDSA]).

Measurements And Main Results: The primary outcome, mean TTR in the first 90 days post-transplant, was 9.

Tacrolimus intrapatient variability in solid organ transplantation: A multiorgan perspective.

Background: Tacrolimus therapy in solid organ transplant (SOT) recipients is challenging due to its narrow therapeutic window and pharmacokinetic variability both between patients and within a single patient. Intrapatient variability (IPV) of tacrolimus trough concentrations has become a novel marker of interest for predicting transplant outcomes. The purpose of this review is to evaluate the association of tacrolimus IPV with graft and patient outcomes and identify interventions to improve IPV in SOT recipients.

Changes in Statin Use Among U.S. Adults With Diabetes: A Population-Based Analysis of NHANES 2011-2018.

Objective: To evaluate statin use in the U.S. before and after the 2015 American Diabetes Association position statement, which expanded statin therapy recommendations to include all adults 40-75 years old with diabetes.

Antithymocyte induction dosing and incidence of opportunistic viral infections using steroid-free maintenance immunosuppression.

Background: Currently, there is limited literature evaluating rATG induction dosing and incidence of opportunistic viral infections when using steroid-free maintenance immunosuppression.

Methods: This single-center, retrospective, study compared high rATG (>4.5 mg/kg) versus low (<4.

Maintenance Immunosuppression in Solid Organ Transplantation: Integrating Novel Pharmacodynamic Biomarkers to Inform Calcineurin Inhibitor Dose Selection.

Calcineurin inhibitors, the primary immunosuppressive therapy used to prevent alloreactivity of transplanted organs, have a narrow therapeutic index. Currently, treatment is individualized based on clinical assessment of the risk of rejection or toxicity guided by trough concentration monitoring. Advances in immune monitoring have identified potential markers that may have value in understanding calcineurin inhibitor pharmacodynamics.

Reducing Donor-specific Antibody During Acute Rejection Diminishes Long-term Renal Allograft Loss: Comparison of Early and Late Rejection.

Background: Reduction in donor-specific antibody (DSA) has been associated with improved renal allograft survival after antibody-mediated rejection (AMR). These observations have not been separately analyzed for early and late AMR and mixed acute rejection (MAR). The purpose of this study was to evaluate long-term responses to proteasome inhibitor-based therapy for 4 rejection phenotypes and to determine factors that predict allograft survival.

Evidence of a clinically significant drug-drug interaction between cannabidiol and tacrolimus.

Cannabidiol (CBD), a major purified nonpsychoactive component of cannabis with anticonvulsant properties, was approved by the U.S. Food and Drug Administration (FDA) in June 2018 as an adjuvant treatment for refractory epilepsy (Epidiolex; GW Pharmaceuticals).

Assessment of tacrolimus intrapatient variability in stable adherent transplant recipients: Establishing baseline values.

The purpose of this study was to determine the intrapatient (within the same patient) variability of tacrolimus in adherent patients. Daily tacrolimus trough levels were obtained at home using dried blood spot technology in kidney and liver transplant recipients. Patients were randomized to receive 3 formulations of tacrolimus, each for two 1-week periods.

Report from the American Society of Transplantation Psychosocial Community of Practice Adherence Task Force: Real-world options for promoting adherence in adult recipients.

Starting in 2015, the American Society of Transplantation Psychosocial Community of Practice, with representatives of the Transplant Pharmacy Community of Practice, convened a taskforce to develop a white paper that focused on clinically practical, evidenced-based interventions that transplant centers could implement to increase adherence to medication and behavioral recommendations in adult solid organ transplant recipients. The group focused on what centers could do in their daily routines to implement best practices to increase adherence in adult transplant recipients. We developed a list of strategies using available resources, clinically feasible methods of screening and tracking adherence, and activities that ultimately empower patients to improve their own self-management.

A phase Ib, open-label, single arm study to assess the safety, pharmacokinetics, and impact on humoral sensitization of SANGUINATE infusion in patients with end-stage renal disease.

The endeavor to study desensitization in kidney transplantation has not been matched by an effort to investigate strategies to prevent sensitization. In this study (NCT02437422), we investigated the safety, impact on sensitization, and pharmacokinetics of SANGUINATE (SG), a hemoglobin-based oxygen carrier, as a potential alternative to packed red blood cells (PRBC) in transplant candidates with end-stage renal disease (ESRD). Ten ESRD subjects meeting inclusion/exclusion (I/E) criteria were planned to receive three weekly infusions of SG (320 mg/kg).

Pharmacokinetic and pharmacogenetic analysis of immunosuppressive agents after laparoscopic sleeve gastrectomy.

Background: Severe obesity has been shown to limit access to renal transplantation in patients with end-stage renal disease (ESRD). Laparoscopic sleeve gastrectomy (LSG) has been performed in the ESRD population to assist in achieving waitlist and transplant eligibility. Little is known about how LSG impacts the bioequivalence of tacrolimus products and immunosuppression pharmacokinetics.