Optimising the Nadroparin Dose for Thromboprophylaxis During Hemodialysis by Developing a Population Pharmacodynamic Model Using Anti-Xa Levels

Autor: Tessa C. C. Jaspers, Charlotte E. Meijer, Louis Jean Vleming, Casper F. M. Franssen, Jeroen Diepstraten, Michael V. Lukens, Patricia M. L. A. van den Bemt, Barbara Maat, Nakisa Khorsand, Daniël J. Touw, Jeroen V. Koomen
Přispěvatelé: Groningen Kidney Center (GKC), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Pharmaceutical Analysis, Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), Medicinal Chemistry and Bioanalysis (MCB), Groningen Research Institute for Asthma and COPD (GRIAC), Biopharmaceuticals, Discovery, Design and Delivery (BDDD)
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Clinical Pharmacokinetics, 61. Springer International Publishing AG
ISSN: 1179-1926
0312-5963
DOI: 10.1007/s40262-022-01162-x
Popis: INTRODUCTION: The optimal nadroparin dose in patients undergoing hemodialysis is difficult to determine in clinical practice. Anti-Xa levels ≥ 0.4 IU/mL and < 2.0 IU/mL are suggested to prevent thrombus formation within the extracorporeal circuit whilst minimizing bleeding risk. We aimed to characterize the variability in the association between dose and anti-Xa levels, identify patient and dialysis characteristics that explained this variability, and optimize nadroparin dosing based on the identified characteristics.METHODS: Anti-Xa samples were collected in patients who received intravenous nadroparin as thromboprophylaxis during routine dialysis sessions. A population pharmacodynamic model was developed using non-linear mixed-effects modelling. The percentage of patients ≥ 0.4 IU/mL (efficacy) and < 2.0 IU/mL (safety) was simulated for different doses, patient and dialysis characteristics.RESULTS: Patients (n = 137) were predominantly receiving standard hemodialysis (84.7% vs. hemodiafiltration 15.3%) and had a mean bodyweight of 76.3 kg (± 16.9). Lean body mass (LBM), mode of dialysis, and dialyzer partially explained between-subject variability in anti-Xa levels. Patients on hemodiafiltration and those receiving hemodialysis with a high LBM (≥ 80 kg) had a low probability (< 29%) of anti-Xa levels ≥ 0.4 IU/mL during the entire dialysis session. All patients, except hemodialysis patients with a low LBM (< 50 kg), had a high probability (> 70%) of peak anti-Xa levels < 2.0 IU/mL.CONCLUSION: Mainly patients receiving hemodiafiltration and those receiving hemodialysis with a high LBM can benefit from a higher nadroparin dose than currently used in clinical practice, while having anti-Xa levels < 2.0 IU/mL.
Databáze: OpenAIRE
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