1. Therapeutic Potential of Citrulline as an Arginine Supplement: A Clinical Pharmacology Review.
- Author
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Rashid, Jahidur, Kumar, Shaun S., Job, Kathleen M., Liu, Xiaoxi, Fike, Candice D., and Sherwin, Catherine M. T.
- Subjects
CITRULLINE ,CLINICAL pharmacology ,ARGININE ,DOSE-response relationship in biochemistry ,PHARMACOKINETICS ,AMINO acids ,PHARMACOLOGY - Abstract
Supplemental arginine has shown promise as a safe therapeutic option to improve endogenous nitric oxide (NO) regulation in cardiovascular diseases associated with endothelial dysfunction. In clinical studies in adults, l-arginine, an endogenous amino acid, was reported to improve cardiovascular function in hypertension, pulmonary hypertension, preeclampsia, angina, and MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) syndrome. l-citrulline, a natural precursor of l-arginine, is more bioavailable than l-arginine because it avoids hepatic first-pass metabolism and has a longer circulation time. Although not yet well-studied, arginine/citrulline has immense therapeutic potential in some life-threatening diseases in children. However, the optimal clinical development of arginine or citrulline in children requires more information about pharmacokinetics and exposure–response relationships at appropriate ages and under relevant disease states. This article summarizes the preclinical and clinical studies of arginine/citrulline in both adults and children, including currently available pharmacokinetic information. The pharmacology of arginine/citrulline is confounded by several patient-specific factors such as variations in baseline arginine/citrulline due to developmental ages and disease states. Currently available pharmacokinetic studies are insufficient to inform the optimal design of clinical studies, especially in children. Successful bench-to-bedside clinical translation of arginine supplementation awaits information from well-designed pharmacokinetic/pharmacodynamic studies, along with pharmacometric approaches. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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