Population kinetics of homoarginine and optimized supplementation for cardiovascular risk reduction
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Population kinetics of homoarginine and optimized supplementation for cardiovascular risk reduction. / Kleist, Christine J; Choe, Chi-Un; Atzler, Dorothee; Schönhoff, Mirijam; Böger, Rainer; Schwedhelm, Edzard; Wicha, Sebastian G.
In: AMINO ACIDS, Vol. 54, No. 6, 06.2022, p. 889-896.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Population kinetics of homoarginine and optimized supplementation for cardiovascular risk reduction
AU - Kleist, Christine J
AU - Choe, Chi-Un
AU - Atzler, Dorothee
AU - Schönhoff, Mirijam
AU - Böger, Rainer
AU - Schwedhelm, Edzard
AU - Wicha, Sebastian G
N1 - © 2022. The Author(s).
PY - 2022/6
Y1 - 2022/6
N2 - 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.
AB - 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.
U2 - 10.1007/s00726-022-03169-x
DO - 10.1007/s00726-022-03169-x
M3 - SCORING: Journal article
C2 - 35618975
VL - 54
SP - 889
EP - 896
JO - AMINO ACIDS
JF - AMINO ACIDS
SN - 0939-4451
IS - 6
ER -
