Kinetic analysis of D-Alanine upon oral intake in humans.

Autor: Kimura T; Department of Nephrology, Osaka University Graduate School of Medicine, Osaka, Japan. t-kimura@kid.med.osaka-u.ac.jp.; Department of Nephrology, Kansai Medical Hospital, Osaka, Japan. t-kimura@kid.med.osaka-u.ac.jp.; Kansai Medical Clinic for Renal Transplantation, Osaka, Japan. t-kimura@kid.med.osaka-u.ac.jp., Sakai S; Department of Nephrology, Osaka University Graduate School of Medicine, Osaka, Japan., Horio M; Department of Nephrology, Kansai Medical Hospital, Osaka, Japan., Takahara S; Kansai Medical Clinic for Renal Transplantation, Osaka, Japan., Ishigo S; KAGAMI INC, Osaka, Japan., Nakane M; KAGAMI INC, Osaka, Japan., Negishi E; KAGAMI INC, Osaka, Japan., Imoto H; KAGAMI INC, Osaka, Japan., Mita M; KAGAMI INC, Osaka, Japan., Hamase K; Department of Drug Discovery and Evolution, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan., Higa-Maekawa Y; Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan., Kakuta Y; Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan., Mizui M; Department of Nephrology, Osaka University Graduate School of Medicine, Osaka, Japan., Isaka Y; Department of Nephrology, Osaka University Graduate School of Medicine, Osaka, Japan.
Jazyk: angličtina
Zdroj: Amino acids [Amino Acids] 2024 Oct 14; Vol. 56 (1), pp. 61. Date of Electronic Publication: 2024 Oct 14.
DOI: 10.1007/s00726-024-03421-6
Abstrakt: D-Alanine, a rare enantiomer of alanine, can potentially alleviate the worsening of viral infections and maintain circadian rhythm. This study aimed to analyze the kinetics of D-Alanine upon oral intake. Five healthy volunteers were administered D-Alanine as a single oral dose at 11,236 or 33,708 µmoL (1-3 g). Upon intake of the lower dose, the plasma level of D-Alanine reached its peak concentration of 588.4 ± 40.9 µM with a peak time of 0.60 ± 0.06 h. The compartment model estimated the clearance of D-Alanine at 12.5 ± 0.3 L/h, or 208 ± 5 mL/min, distribution volume of 8.3 ± 0.7 L and half-life of 0.46 ± 0.04 h, suggesting a rapid clearance of D-Alanine. The peak concentration and area under the curve increased proportionally upon intake of the higher dose, while the clearance, distribution volume and half-life did not. The urinary ratio of D-Alanine per sum of D- and L-Alanine reached its peak of nearly 100%, followed by a slow decline. The peak time of the urinary ratio was 1.15 ± 0.15 h, showing a time lag of blood to urine excretion. Fractional excretion, a ratio of the clearance of a substance per a standard molecule in kidney, of D-Alanine increased from 14.0 ± 5.8% to 64.5 ± 10.3%; the latter corresponded to the urinary clearance of D-Alanine as about 77 mL/min for an adult, with a peak time of 1.90 ± 0.56 h. D-Alanine was quickly absorbed and appeared in blood, followed by urinary excretion. This kinetic analysis increases our fundamental knowledge of the oral intake of D-Alanine for the chronic dosing. Trial number: #UMIN000050865. Date of registration: 2023/6/30.
(© 2024. The Author(s).)
Databáze: MEDLINE
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