Pharmacokinetics of theanine enantiomers in rats

Theanine, first discovered in tea, is a chiral nonproteinic amino acid that has been reported to have cardiovascular, neurological, and oncological effects. It is being considered as a therapeutic/medicinal agent and additive in consumer products. The present study evaluated the pharmacokinetics of d ‐theanine, l ‐theanine, and d , l ‐theanine in plasma and urine using LC‐ESI/MS in rats after oral (p.o.) and intraperitoneal (i.p.) administration. Oral administration data indicated that gut absorption of d ‐theanine was far less than that of l ‐theanine. However, after i.p. administration, plasma theanine concentrations of l ‐ and d ‐theanine were similar. This indicated that d ‐ and l ‐theanine may exhibit a competitive effect with respect to intestinal absorption. Regardless of the route of administration, p.o. or i.p., the presence of the other enantiomer always decreased theanine plasma concentrations, indicating d , l ‐theanine competition with respect to urinary reabsorption. Data on urinary concentrations of d ‐theanine suggested that the d ‐isomer may be eliminated with minimal metabolism. l ‐Theanine appeared to be preferentially reabsorbed and metabolized by the kidney while d ‐theanine was preferentially excreted. Clearly, the bioequivalencies of d , l ‐theanine and its enantiomers were found to be quite different from one another. Consequently, the efficacy of commercial theanine products containing d ‐theanine, l ‐theanine, or d , l ‐theanine may be quite different. Chirality 17:154–162, 2005. © 2005 Wiley‐Liss, Inc.