Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2024, 168(2):117-123 | DOI: 10.5507/bp.2022.048

Novel approach to adherence assessment based on parent drug and metabolite pharmacokinetics: pilot study with spironolactone

Alena Pilkova1, Martin Sima1, Jan Miroslav Hartinger1, Thi Minh Phuong Nikrynova Nguyen2, Vera Maresova3, Ivana Kurcova3, Ondrej Slanar1, Jiri Widimsky2
1 Department of Clinical Pharmacology and Pharmacy, Institute of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic
2 Third Internal Department of Endocrinology and Metabolism, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic
3 Institute of Forensic Medicine and Toxicology, Toxicology Laboratory, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic

Aim: The aim of this study was to evaluate adherence to spironolactone in a group of unselected patients with arterial hypertension by analysis of measured serum spironolactone and canrenone concentrations according to a proposed two-step decision scheme based on pharmacokinetic considerations.

Materials and Methods: Simulation of serum concentration-time profiles of spironolactone and canrenone based on population pharmacokinetic parameters described in literature and a body weight-normalized spironolactone dose / canrenone level nomogram derived from a group of adherent patients with conservatively treated primary hyperaldosteronism, were used to create a two-step decision scheme. 71 outpatients treated with spironolactone for resistant hypertension with spironolactone and canrenone serum concentrations measured between 2018 and 2021 were analyzed according to the proposed scheme. We compared our proposed methodology to the standard approach for adherence testing.

Results: With the most sensitive traditional approach to adherence assessment through detectable serum concentrations of spironolactone and/or canrenone, 9 (12.7%) non-adherent patients were identified. With our two-step assessment of adherence, we were able to identify 18 (25.4%) non-adherent patients.

Conclusion: Consideration of the pharmacokinetic properties of parental drug and its metabolite led to improved sensitivity in non-adherence detection in patients with arterial hypertension. This approach enables better interpretation of measured spironolactone and canrenone serum concentrations and should be used in clinical practice.

Keywords: drug monitoring, pharmacokinetics, hypertension, laboratories, hospital

Received: October 4, 2022; Revised: November 6, 2022; Accepted: November 14, 2022; Prepublished online: December 2, 2022; Published: June 10, 2024  Show citation

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Pilkova, A., Sima, M., Hartinger, J.M., Nikrynova Nguyen, T.M.P., Maresova, V., Kurcova, I., Slanar, O., & Widimsky, J. (2024). Novel approach to adherence assessment based on parent drug and metabolite pharmacokinetics: pilot study with spironolactone. Biomedical papers, 168(2), 117-123. doi: 10.5507/bp.2022.048
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