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Population pharmacokinetics of ramipril in patients with chronic heart failure : a real-world longitudinal study
ID
Čvan Trobec, Katja
(
Author
),
ID
Grabnar, Iztok
(
Author
),
ID
Trontelj, Jurij
(
Author
),
ID
Lainščak, Mitja
(
Author
),
ID
Kerec Kos, Mojca
(
Author
)
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Abstract
In patients with chronic heart failure (CHF), the use of angiotensinconverting 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 glomerular 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.
Language:
English
Keywords:
ramipril
,
ramiprilat
,
pharmacokinetics
,
chronic heart failure
,
body composition
Work type:
Article
Typology:
1.01 - Original Scientific Article
Organization:
FFA - Faculty of Pharmacy
Publication status:
Published
Publication version:
Version of Record
Year:
2024
Number of pages:
Str. 315-328
Numbering:
Vol. 74, no. 2
PID:
20.500.12556/RUL-158260
UDC:
615.015:616.12-008.46
ISSN on article:
1846-9558
DOI:
10.2478/acph-2024-0018
COBISS.SI-ID:
194982915
Publication date in RUL:
31.05.2024
Views:
208
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49
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Title:
Acta pharmaceutica
Shortened title:
Acta pharm.
Publisher:
Croatian Pharmaceutical Society
ISSN:
1846-9558
COBISS.SI-ID:
3817585
Licences
License:
CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
Link:
http://creativecommons.org/licenses/by-nc-nd/4.0/
Description:
The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.
Secondary language
Language:
Slovenian
Keywords:
farmakokinetika
,
srčno popuščanje
,
ramipril
,
ramiprilat
,
kronično srčno popuščanje
,
telesna sestava
Projects
Funder:
ARIS - Slovenian Research and Innovation Agency
Project number:
P1-0189
Name:
Farmacevtska tehnologija: od dostavnih sistemov učinkovin do terapijskih izidov zdravil pri otrocih in starostnikih
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