Population kinetics of homoarginine and optimized supplementation for cardiovascular risk reduction.
Amino acids
Cardiovascular disease
Homoarginine
Kinetic
Pharmacometrics
Population pharmacokinetics
Journal
Amino acids
ISSN: 1438-2199
Titre abrégé: Amino Acids
Pays: Austria
ID NLM: 9200312
Informations de publication
Date de publication:
Jun 2022
Jun 2022
Historique:
received:
22
12
2021
accepted:
01
05
2022
pubmed:
27
5
2022
medline:
24
6
2022
entrez:
26
5
2022
Statut:
ppublish
Résumé
Homoarginine is an endogenous amino acid whose levels are reduced in patients with renal, cardio- and cerebrovascular disease. Moreover, low homoarginine concentrations independently predict morbidity and mortality in these patients. Besides endogenous synthesis, homoarginine is also a constituent of the human diet. The objective of the present study was to analyze the kinetics of orally supplemented homoarginine in human plasma by means of a pharmacometric approach. We developed a pharmacometric model to evaluate different dosing regimens, especially the regimen of 125 mg once weekly, based on a previous clinical study (n = 20). The model was adapted to account for differences in baseline homoarginine plasma concentrations between healthy and diseased individuals. A novel dosing regimen of 25 mg once daily led to higher attainment of homoarginine reference concentrations using clinical trial simulations. With 25 mg/day, the trough concentration of only 6% of the older and 3.8% of the younger population was predicted to be below the target concentration of 2.0-4.1 µmol/L. In synopsis, the new dosing regimen recapitulates the kinetics of homoarginine in healthy individuals optimally.
Identifiants
pubmed: 35618975
doi: 10.1007/s00726-022-03169-x
pii: 10.1007/s00726-022-03169-x
pmc: PMC9213336
doi:
Substances chimiques
Homoarginine
156-86-5
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
889-896Informations de copyright
© 2022. The Author(s).
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