Kinetic analysis of D-Alanine upon oral intake in humans

• Published in: Amino acids 2024-10, Vol.56 (1), p.61-8, Article 61
• Main Authors: Kimura, Tomonori, Sakai, Shinsuke, Horio, Masaru, Takahara, Shiro, Ishigo, Shoto, Nakane, Maiko, Negishi, Eiichi, Imoto, Hiroshi, Mita, Masashi, Hamase, Kenji, Higa-Maekawa, Yoko, Kakuta, Yoichi, Mizui, Masayuki, Isaka, Yoshitaka
• Format: Article
• Language: English
• Subjects: Administration, Oral; Adult; Alanine; Alanine - blood; Alanine - pharmacokinetics; Amino acids; Analytical Chemistry; Biochemical Engineering; Biochemistry; Biomedical and Life Sciences; Blood; Circadian rhythm; Circadian rhythms; Clearance; COVID-19; D-Alanine; Distribution; Dosage; Drug dosages; Enantiomers; Excretion; Female; Half-Life; Healthy Volunteers; Humans; Infections; Influenza; Kidney diseases; Kinetics; L-Alanine; Life Sciences; Male; Nephrology; Neurobiology; Original; Original Article; Pharmacokinetics; Proteomics; Stereoisomerism; Time lag; Urinary excretion; Urine; Viral infections; Young Adult
• ISSN: 1438-2199; 0939-4451; 1438-2199
• DOI: 10.1007/s00726-024-03421-6

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.