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Supplement: 6^th Amino Acid Assessment Workshop: SESSION 2

Pharmacokinetics of Arginine and Related Amino Acids^1–3,

Clinical Chemistry Laboratory, Hôtel-Dieu Hospital, AP-HP, Paris, France, and Laboratory of Biological Nutrition EA 2498, Faculty of Pharmacy, University Paris 5 René Descartes, Paris 75006, France

^* To whom correspondence should be addressed. E-mail: luc.cynober{at}htd.aphp.fr.

Arginine (ARG) and its related amino acids (AAs) ornithine (ORN) and citrulline (CIT) find a range of applications as dietary supplements in subgroups of healthy subjects (e.g., bodybuilders) and patients with acute or chronic malnutrition. These AAs appear to be well utilized in humans with, in general, a rapid return of blood concentrations to basal values (i.e., within 5–8 h) and low absolute and relative excretion in urine (< 5% of administered dose). Based on published data for the maximum observed plasma concentrations (C_max) after administration of doses in the range 5 to 10 g, CIT appeared to present relatively better absorption and systemic bioavailability than ARG and ORN. The few relevant dose-ranging studies available include 1 limited to a single subject receiving 5- to 20-g doses of ornithine -ketoglutarate and another in which 8 subjects received from 5 to 15 g of CIT. Comparison of these 2 studies further indicates that CIT has higher bioavailability than ORN. The pharmacokinetics and metabolism of these AAs are modified by the coadministration of a salt such as -ketoglutarate that modifies AA metabolism, as has clearly been demonstrated for ornithine -ketoglutarate. Concomitant administration of a meal leads to a 15- to 30-min delay in C_max. Finally, data from various pharmacokinetic studies together with basic physiology and biochemistry indicate that ARG is a net urea producer and ORN has a nitrogen-sparing effect, whereas CIT is neutral. However, most of the studies performed to date carry methodological weaknesses and are difficult to compare because of a number of confounding factors. To date, there have been no pharmacokinetic studies on the long-term administration of these AAs in healthy subjects despite the need to determine the safe upper limit of daily intake.