Population pharmacokinetics of ramipril in patients with chronic heart failure: A real-world longitudinal study
Author:
Trobec Katja Čvan1, Grabnar Iztok1ORCID, Trontelj Jurij1, Lainščak Mitja23ORCID, Kos Mojca Kerec1ORCID
Affiliation:
1. University of Ljubljana Faculty of Pharmacy Ljubljana , Slovenia 2. Faculty of Medicine , University of Ljubljana Ljubljana , Slovenia 3. Division of Cardiology General Hospital Murska Sobota , Murska Sobota Slovenia
Abstract
Abstract
In patients with chronic heart failure (CHF), the use of angiotensin-converting enzyme inhibitors, including ramipril, is recommended to reduce the risk of heart failure worsening, hospitalisation, and death. Our aim was to investigate the influence of body composition on the pharmacokinetics of ramipril and its active metabolite ramiprilat and to evaluate the changes in pharmacokinetics after prolonged therapy. Twenty-three patients with CHF who were on regular therapy with ramipril participated at the first study visit ( median age 77 years, 65 % male, and 70 % New York Heart Association Class II); 19 patients attended the second study visit and the median time between the two visits was 8 months. Pharmacokinetics were assessed using a nonlinear mixed-effects parent-metabolite model comprising two compartments for ramipril and one compartment for ramiprilat. The influence of body size and composition was best described by an allometric relationship with fat-free mass. In addition, ramipril clearance was related to patient age and daily ramipril dose, while clearance of ramiprilat was influenced by glome rular filtration rate and daily ramipril dose. There were no clinically relevant changes in the pharmacokinetics of ramipril and ramiprilat between the study visits. Due to the relatively stable pharmacokinetics of ramipril, regular outpatient visits at 6-month intervals seem appropriate to evaluate ramipril therapy.
Publisher
Walter de Gruyter GmbH
Reference33 articles.
1. S. Stewart, I. Ekman, T. Ekman, A. Oden and A. Rosengren, Population impact of heart failure and the most common forms of cancer: a study of 1 162 309 hospital cases in Sweden (1988 to 2004), Circ. Cardiovasc. Qual. Outcomes 3(6) (2010) 573-580 2. S. Stewart, I. Ekman, T. Ekman, A. Oden and A. Rosengren, Population impact of heart failure and the most common forms of cancer: a study of 1 162 309 hospital cases in Sweden (1988 to 2004), Circ. Cardiovasc. Qual. Outcomes 3 3. (6) (2010) 573-580; https://doi.org/10.1161/CIRCOUTCOMES.110.957571 4. T. A. McDonagh, M. Metra, M. Adamo, R. S. Gardner, A. Baumbach, M. Böhm, H. Burri, J. Butler, J. Čelutkienė, O. Chioncel, J. G. F. Cleland, A. J. S. Coats, M. G. Crespo-Leiro, D. Farmakis, M. Gi-lard, S. Heymans, A. W. Hoes, T. Jaarsma, E. A. Jankowska and A. K. Skibelund, 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure, Eur. Heart J. 42(36) (2021) 3599-3726 5. T. A. McDonagh, M. Metra, M. Adamo, R. S. Gardner, A. Baumbach, M. Böhm, H. Burri, J. Butler, J. Čelutkienė, O. Chioncel, J. G. F. Cleland, A. J. S. Coats, M. G. Crespo-Leiro, D. Farmakis, M. Gi-lard, S. Heymans, A. W. Hoes, T. Jaarsma, E. A. Jankowska and A. K. Skibelund, 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure, Eur. Heart J. 42
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