Therapeutic drug monitoring of tacrolimus and mycophenolic acid in outpatient renal transplant recipients using a volumetric dried blood spot sampling device

Zwart, Tom C.; Gokoel, Sumit R.M.; Boog, Paul J.M. van der; Fijter, Johan W. de; Kweekel, Dina M.; Swen, Jesse J.; Guchelaar, Henk‐Jan; Moes, Dirk Jan A R

doi:10.1111/bcp.13755

Cited by 76 publications

(102 citation statements)

References 58 publications

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“…In accordance with other studies, acceptable values for MPPE and MAPE were set at <15% and at least 67% of all samples should have an absolute prediction error of <20% [5,20].…”

Section: Discussionsupporting

confidence: 53%

“…To the best of our knowledge, no guideline is available to determine limits of clinical relevance for DBS. The available literature suggests that setting a limit of clinical relevance should be done in a multidisciplinary team taking into account the clinical application of the method, the patient characteristics and the properties of the analytical methods [5,20]. In our study, the everolimus DBS method does not meet the limits of clinical relevance set by our team and, at this time, cannot replace conventional WB sampling in the TDM of transplant patients where low trough concentrations are targeted.…”

Section: Discussionmentioning

confidence: 90%

“…Other clinical validation studies usually have few samples and very few samples in the low concentrations range. However, in a study on tacrolimus, 22.2% (n = 63) of the lower (trough) concentrations exceeded ±20% limits of the DBS to WB concentration ratio [5]. In this study, the area under the curve (AUC) was calculated for both DBS and WB based on trough concentrations and three sampling points at t = 1, t = 2 and t = 3 h after medication intake.…”

Section: Discussionmentioning

confidence: 95%

“…Traditionally, venous blood samples are used for monitoring of immunosuppressive drug concentrations and patients have to travel to the hospital on a regular basis to have their blood drawn. To decrease the burden for patients, dried blood spot (DBS) home sampling has been developed among various micro sampling methods for several drugs, including immunosuppressants, to enable home sampling [5][6][7][8][9][10][11][12][13][14][15][16]. For this, a drop of blood from a fingerprick is applied to a sampling card and dried.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, a clinical validation study showing interchangeability between DBS and venous sampling is required before clinical application [18]. This is shown for tacrolimus, cyclosporin A and creatinine [5,[7][8][9][10][11][12][13][14][15]19]. For sirolimus, Dickerson et al report agreement between fingerprick DBS and venous samples in 25 pediatric transplant patients, where mean DBS concentrations were on average 0.8 μg/L lower than venous samples [15].…”

Section: Introductionmentioning

confidence: 99%

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Clinical application of a dried blood spot assay for sirolimus and everolimus in transplant patients

Veenhof

Koster²,

Alffenaar

et al. 2019

Clinical Chemistry and Laboratory Medicine (CCLM)

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Background Monitoring of immunosuppressive drugs such as everolimus and sirolimus is important in allograft rejection prevention in transplant patients. Dried blood spots (DBS) sampling gives patients the opportunity to sample a drop of blood from a fingerprick at home, which can be sent to the laboratory by mail. Methods A total of 39 sirolimus and 44 everolimus paired fingerprick DBS and whole blood (WB) samples were obtained from 60 adult transplant patients for method comparison using Passing-Bablok regression. Bias was assessed using Bland-Altman. Two validation limits were pre-defined: limits of analytical acceptance were set at >67% of all paired samples within 20% of the mean of both samples and limits of clinical relevance were set in a multidisciplinary team at >80% of all paired samples within 15% of the mean of both samples. Results For both sirolimus and everolimus, Passing-Bablok regression showed no differences between WB and DBS with slopes of 0.86 (95% CI slope, 0.72–1.02) and 0.96 (95% CI 0.84–1.06), respectively. Only everolimus showed a significant constant bias of 4%. For both sirolimus and everolimus, limits of analytical acceptance were met (76.9% and 81.8%, respectively), but limits or clinical relevance were not met (77.3% and 61.5%, respectively). Conclusions Because pre-defined limits of clinical relevance were not met, this DBS sampling method for sirolimus and everolimus cannot replace WB sampling in our center at this time. However, if the clinical setting is compatible with less strict limits for clinical relevance, this DBS method is suitable for clinical application.

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“…In accordance with other studies, acceptable values for MPPE and MAPE were set at <15% and at least 67% of all samples should have an absolute prediction error of <20% [5,20].…”

Section: Discussionsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Clinical application of a dried blood spot assay for sirolimus and everolimus in transplant patients

Veenhof

Koster²,

Alffenaar

et al. 2019

Clinical Chemistry and Laboratory Medicine (CCLM)

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Therapeutic Drug Monitoring

2020

Fundamentals of Analytical Toxicology

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To study the appropriateness of phlebotomy for digoxin therapeutic drug monitoring (TDM) in outpatients, we conducted a retrospective chart review, a computer search of all previous TDM testing, and a questionnaire of all outpatients (n = 86) who had serum digoxin determinations between April 10 and April 28, 1992 (585 tests). In patients who took digoxin at the same time daily (40 patients, 300 tests), 52% of tests were performed on inappropriate samples drawn within 6 h of the last dose. No patient who took digoxin after 1700 had inappropriate tests. Phlebotomy for serum digoxin determinations before distribution of digoxin is complete is a common problem in outpatients, leading to clinically uninterpretable test results. Postdistribution sampling can be assured by nighttime dosing, and this recommendation has been implemented at our hospital. INDEXING TERMS: blood sampling #{149} pharmacokinetics Digoxin is one of the most widely prescribed drugs for both inpatients and outpatients /1], and digoxin serum concentration is the most commonly ordered therapeutic drug monitoring (TDM) test in the US. Digoxin serum concentrations have been shown to be useful in corroborating the clinical diagnosis of digoxin toxicity as well as correlating with therapeutic effects of digoxin [2, 3]. Digoxin pharmacokinetics are complex hut well characterized (for a review see [4]). For oral dosing of digoxin, rapid absorption occurs in the intestine /4/; reaching distributional equilibrium after a digoxin dose requires at least 8 h, the time at which the semilog plots of plasma and tissue concentrations vs time reach terminal linear and parallel slopes [4, 5]. Samples obtained within 8 h after a digoxin dose can be very misleading as an index of digoxin response /4/.

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Tacrolimus and Mycophenolic Acid Exposure Are Associated with Biopsy‐Proven Acute Rejection: A Study to Provide Evidence for Longer‐Term Target Ranges

Meziyerh

Gelder

Kers

et al. 2023

Clin Pharma and Therapeutics

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Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?; There is scant evidence for long-term targets for maintenance immunosuppression after kidney transplantation. Therefore, the therapeutic window for tacrolimus (Tac) and mycophenolic acid (MPA) beyond the first year of transplantation is mainly extrapolated from trials limited to the first year that did not consider simultaneous exposure. WHAT QUESTION DID THIS STUDY ADDRESS?; The primary and secondary objectives were to (i) investigate the relationship between simultaneous exposure to Tac/MPA and biopsy-proven acute rejection (BPAR), and (ii) explore a lower threshold of the target range. WHAT THIS STUDY ADDS TO OUR KNOWLEDGE?; Using Cox regression and joint models, we showed that TAC/MPA exposure is significantly associated with BPAR beyond the first year of transplantation.; A Tac-area under the curve from zero to 12 hours (AUC 0-12h ) 75-95 ng*hour/mL, Tac-trough levels 5-7 ng/mL, and MPA-AUC 0-12h 30-60 mg*hour/L might be suggested as optimal targets between the first and third years. HOW MIGHT THIS CHANGE CLINICAL PHARMA-COLOGY OR TRANSLATIONAL SCIENCE?; These results provide evidence on the long-term lower threshold of the target range. This may aid physicians in determining the longer-term therapeutic window of Tac/MPA in kidney transplantation.

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Therapeutic drug monitoring of tacrolimus and mycophenolic acid in outpatient renal transplant recipients using a volumetric dried blood spot sampling device

Cited by 76 publications

References 58 publications

Clinical application of a dried blood spot assay for sirolimus and everolimus in transplant patients

Clinical application of a dried blood spot assay for sirolimus and everolimus in transplant patients

Therapeutic Drug Monitoring

Tacrolimus and Mycophenolic Acid Exposure Are Associated with Biopsy‐Proven Acute Rejection: A Study to Provide Evidence for Longer‐Term Target Ranges

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