Population kinetics of homoarginine and optimized supplementation for cardiovascular risk reduction

Kleist, Christine J.; Choe, Chi-Un; Atzler, Dorothee; Schoenhoff, Mirjam; Böger, Rainer; Schwedhelm, Edzard und Wicha, Sebastian G. (2022): Population kinetics of homoarginine and optimized supplementation for cardiovascular risk reduction. In: Amino Acids, Bd. 54, Nr. 6: S. 889-896

Abstract

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 mu mol/L. In synopsis, the new dosing regimen recapitulates the kinetics of homoarginine in healthy individuals optimally.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0939-4451
• Sprache: Englisch