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Kinetical analysis of D-alanine upon oral intake

Kimura, T.; Sakai, S.; Horio, M.; Takahara, S.; Ishigo, S.; Nakane, M.; Negishi, E.; Imoto, H.; Mita, M.; Hamase, K.; Higa-Maekawa, Y.; Kakuta, Y.; Mizui, M.; Isaka, Y.

2024-05-21 nephrology
10.1101/2024.05.21.24307633 medRxiv
Show abstract

D-Alanine, a rare enantiomer of alanine in life, 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 12,366 or 33,708 moL. Upon intake of the lower dose, the plasma level of D-alanine reached its peak concentration of 588.4 {+/-} 40.9 M with a peak time of 0.60 {+/-} 0.06 h. The plasma level of D-alanine became close to the endogenous level after 24 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. 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 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 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.

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