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

Autor: Zwart TC; Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Albinusdreef 2, 2333, ZA, Leiden, the Netherlands., Gokoel SRM; Department of Nephrology, Leiden University Medical Center, Albinusdreef 2, 2333, ZA, Leiden, the Netherlands., van der Boog PJM; Department of Nephrology, Leiden University Medical Center, Albinusdreef 2, 2333, ZA, Leiden, the Netherlands., de Fijter JW; Department of Nephrology, Leiden University Medical Center, Albinusdreef 2, 2333, ZA, Leiden, the Netherlands., Kweekel DM; Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Albinusdreef 2, 2333, ZA, Leiden, the Netherlands., Swen JJ; Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Albinusdreef 2, 2333, ZA, Leiden, the Netherlands., Guchelaar HJ; Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Albinusdreef 2, 2333, ZA, Leiden, the Netherlands., Moes DJAR; Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Albinusdreef 2, 2333, ZA, Leiden, the Netherlands.
Jazyk: angličtina
Zdroj: British journal of clinical pharmacology [Br J Clin Pharmacol] 2018 Dec; Vol. 84 (12), pp. 2889-2902. Date of Electronic Publication: 2018 Oct 15.
DOI: 10.1111/bcp.13755
Abstrakt: Aims: Tacrolimus and mycophenolic acid dosing after renal transplantation is individualized through therapeutic drug monitoring (TDM). Home-based dried blood spot (DBS) sampling has the potential to replace conventional TDM sampling at the clinic. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay was developed to quantify tacrolimus and mycophenolic acid in DBS and clinically validated for abbreviated area under the concentration-time curve (AUC) monitoring using an innovative volumetric DBS sampling device.
Methods: Clinical validation was performed by direct comparison of paired DBS and whole blood (WB) (tacrolimus) and plasma (mycophenolic acid) concentrations and AUCs. Agreement was evaluated using Passing-Bablok regression, Bland-Altman analysis and DBS-to-WB predictive performance. TDM dosing recommendations based on both methods were compared to assess clinical impact.
Results: Paired tacrolimus (n = 200) and mycophenolic acid (n = 192) DBS and WB samples were collected from 65 kidney(-pancreas) transplant recipients. Differences for tacrolimus and mycophenolic acid were within ±20% for 84.5% and 76.6% of concentrations and 90.5% and 90.7% of AUCs, respectively. Tacrolimus and mycophenolic acid dosing recommendation differences occurred on 44.4% and 4.7% of occasions. Tacrolimus DBS dosing recommendations were 0.35 ± 0.14 mg higher than for WB and 8 ± 3% of the initial dose. Mycophenolic acid DBS dosing recommendations were 23.3 ± 31.9 mg lower than for plasma and 2 ± 3.5% of the initial dose.
Conclusions: Tacrolimus and mycophenolic acid TDM for outpatient renal transplant recipients, based on abbreviated AUC collected with a DBS sampling device, is comparable to conventional TDM based on WB sampling. Patient training and guidance on good blood-spotting practices is essential to ensure method feasibility.
(© 2018 The British Pharmacological Society.)
Databáze: MEDLINE
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