Dataset Information

Population kinetics of homoarginine and optimized supplementation for cardiovascular risk reduction.

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

SUBMITTER: Kleist CJ

PROVIDER: S-EPMC9213336 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Population kinetics of homoarginine and optimized supplementation for cardiovascular risk reduction.

Kleist Christine J CJ Choe Chi-Un CU Atzler Dorothee D Schönhoff Mirjam M Böger Rainer R Schwedhelm Edzard E Wicha Sebastian G SG

Amino acids 20220526 6

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 pharmacometri ...[more]

PMID: 35618975

Similar Datasets

Project description:BackgroundDecreased physical activity had been reported to be a common causal and modifiable risk factor for major vascular events. However, the relationship of physical activity and sedentary leisure time with carotid atherosclerosis in population with high risk for cardiovascular diseases (CVDs) is still inconclusive. We aimed to evaluate the association of physical activity and sedentary leisure time with the risk of carotid atherosclerosis, and investigate any possible effect modifiers in population with high risk for CVDs.MethodsThe study population was drawn from the China Patient-Centered Evaluative Assessment of Cardiac Events (PEACE) Million Persons Project-Jiangsu project, which is a population-based screening project that included permanent residents aged 35-75 years from 6 surveillance cities in Jiangsu Province. Linear regression models were used to evaluate the association of physical activity and sedentary leisure time with carotid intima-media thickness (CIMT). The risks of abnormal carotid artery and carotid plaque (CP) were estimated by odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression.ResultsOverall, a total of 10,920 participants were enrolled in the final analysis. There was a significant inverse association of physical activity level with CIMT (per SD increase: β=-0.0103; 95%CI: -0.0154, -0.0053). The risk of abnormal carotid artery and CP decreased significantly with the increase of physical activity level (per SD increase: OR=0.908, 95%CI: 0.869-0.948; OR=0.900, 95%CI: 0.857-0.945, respectively). When physical activity level was categorized as quartiles, a significantly lower risk of abnormal carotid artery and CP was found in quartiles 2-4 with quartile 1 as reference (P<0.05 for all). Furthermore, the inverse association were stronger in participants with age ≥60 years (vs. <60 years, Pinteraction<0.001 for both). However, there were no significant association of sedentary leisure time with CIMT, abnormal carotid artery and CP.ConclusionsIn population with high risk for CVDs, physical activity was inversely associated with CIMT, abnormal carotid artery and CP, particularly among the elders. Sedentary leisure time was not associated with them. These results suggested that physical activity is important for carotid vascular health, and perhaps especially in elder population.

Dataset Information

Population kinetics of homoarginine and optimized supplementation for cardiovascular risk reduction.

Publications

Population kinetics of homoarginine and optimized supplementation for cardiovascular risk reduction.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets