Unequal hydrolysis of salicylic acid-D-alanine and salicylic acid-L-alanine conjugate in rabbit intestinal microorganisms.
The behavior of salicylic acid-D-alanine conjugate (salicyl-D-alanine) following intravenous, oral and intracecal administration was examined in rabbits, then compared with that of salicylic acid-L-alanine conjugate (salicyl-L-alanine) as reported previously. Following intravenous administration, salicyl-D-alanine eliminated rapidly from the blood, and its blood concentration was almost identical with that of salicyl-L-alanine. In both cases, salicylic acid could not be detected in the blood, indicating that systemic de-conjugation of D-alanine might not occur. Unchanged salicyl-D-alanine was found in the blood mainly following oral and intracecal administration of salicyl-D-alanine. On the other hand, salicylic acid formed extensively following oral and intracecal administration of salicyl-L-alanine, suggesting that the presystemic de-conjugation of D-alanine and L-alanine was unequal. Furthermore, in vitro incubation of salicyl-D-alanine with cecal content, in which the major source of salicyl-L-alanine hydrolysis is found, showed that the hydrolysis of salicyl-D-alanine was negligible in rabbit intestinal microorganisms.
Nakamura
J
J
School of Pharmaceutical Sciences, Nagasaki University, Japan.
Tagami
C
C
Nishida
K
K
Sasaki
H
H
D000284:Administration, Oral; D000409:Alanine / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D000818:Animals; D001419:Bacteria / Q000378:metabolism*; D002432:Cecum / Q000382:microbiology*; D006868:Hydrolysis; D007275:Injections, Intravenous; D008297:Male; D011817:Rabbits; D012459:Salicylates / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D013237:Stereoisomerism
D012459:Salicylates; C075130:salicylic acid-alanine conjugate; D000409:Alanine