Intestinal Microorganisms

14,000,000 Leading Edge Experts on the ideXlab platform

Scan Science and Technology

Contact Leading Edge Experts & Companies

Scan Science and Technology

Contact Leading Edge Experts & Companies

The Experts below are selected from a list of 2097 Experts worldwide ranked by ideXlab platform

Hitoshi Sasaki - One of the best experts on this subject based on the ideXlab platform.

  • Pharmacokinetic Analysis of In Vivo Metabolism of Amino Acid or Dipeptide Conjugates of Salicylic Acid in Rabbit Intestinal Microorganisms
    2015
    Co-Authors: Koyo Nishida, Hitoshi Sasaki, Mitsuhiko Kido, Junzo Nakamura
    Abstract:

    We analyzed the pharmacokinetics of salicylic acid (SA)-amino acid (alanine, glutamic acid, methionine and tyrosine) or-dipeptide (glycylglycine) conjugates in rabbits, by using a model that takes into account the metabolism of prodrug to SA by Intestinal Microorganisms, and also by model-independent analysis. The blood concentration profiles of these prodrugs and released SA following intracecal and oral administration to rabbits were obtained previously (Nakamura et al., J. Pharm. Pharmacol., 44, 295-299

  • Pharmacokinetic Analysis of In Vivo Metabolism of Amino Acid or Dipeptide Conjugates of Salicylic Acid in Rabbit Intestinal Microorganisms
    Pharmaceutical research, 1994
    Co-Authors: Koyo Nishida, Hitoshi Sasaki, Mitsuhiko Kido, Junzo Nakamura
    Abstract:

    We analyzed the pharmacokinetics of salicylic acid (SA)-amino acid (alanine, glutamic acid, methionine and tyrosine) or -dipeptide (glycylglycine) conjugates in rabbits, by using a model that takes into account the metabolism of prodrug to SA by Intestinal Microorganisms, and also by model-independent analysis. The blood concentration profiles of these prodrugs and released SA following intracecal and oral administration to rabbits were obtained previously (Nakamura et al., J. Pharm. Pharmacol., 44, 295-299, 1992; Chem. Pharm. Bull., 40, 2164-2168, 1992; Int. J. Pharm., 87, 59-66, 1992; J. Pharm. Pharmacol., 44, 713-716, 1992). First, the overall in vivo behaviour was evaluated by statistical moment analysis. Next, the blood concentration profiles of prodrug and SA following intracecal and oral administration were simultaneously fitted to the above model. In general, good agreement was observed between fitted lines and experimental data for every prodrug, suggesting the validity of this model. The obtained parameters characterized the difference in the rate of metabolism and absorption among the prodrugs. Lower absorbability and enhanced hydrolysis rate of the prodrug lead to prolonged blood concentration of SA.

  • A novel prodrug of salicylic acid, salicylic acid-glycylglycine conjugate, utilizing the hydrolysis in rabbit Intestinal Microorganisms.
    Journal of Pharmacy and Pharmacology, 1992
    Co-Authors: Junzo Nakamura, Koyo Nishida, Kumiko Asai, Hitoshi Sasaki
    Abstract:

    The hydrolysis of salicylic acid-glycylglycine conjugate (salicyl-glycylglycine) following oral, intravenous, intracaecal and rectal administration (434, 72, 36 and 36 mumol kg-1, respectively: equivalent to salicylic acid) was examined in rabbits to develop a novel prodrug of salicylic acid. Salicylic acid was detected in the blood 2 h after oral administration of salicyl-glycylglycine and it reached a maximum level (55.6 micrograms mL-1) at 15 h, whereas a small amount of salicyl-glycylglycine was found in the blood. In contrast, unchanged salicyl-glycylglycine was found mainly in the blood following its intravenous administration, suggesting the involvement of presystemic deconjugation in the hydrolysis of salicyl-glycylglycine. Immediate and very extensive salicyclic acid formation in the caecum was observed following intracaecal administration of salicyl-glycylglycine, suggesting that the Intestinal Microorganisms were responsible for the biotransformation of this compound. In-vitro incubation of salicyl-glycylglycine with caecal content showed that salicyl-glycylglycine was hydrolysed efficiently in the caecum. Consequently, the blood concentration of salicylic acid was prolonged extensively following rectal administration of salicyl-glycylglycine, indicating the usefulness of salicyl-glycylglycine as a prodrug of salicylic acid.

  • Unequal hydrolysis of salicylic acid-D-alanine and salicylic acid-L-alanine conjugate in rabbit Intestinal Microorganisms.
    Chemical & Pharmaceutical Bulletin, 1992
    Co-Authors: Junzo Nakamura, Chieko Tagami, Koyo Nishida, Hitoshi Sasaki
    Abstract:

    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.

  • Effect of oral pretreatment with antibiotics on the hydrolysis of salicylic acid-tyrosine and salicylic acid-methionine prodrugs in rabbit Intestinal Microorganisms.
    Chemical & pharmaceutical bulletin, 1992
    Co-Authors: Junzo Nakamura, Koyo Nishida, Mitsuhiko Kido, Hitoshi Sasaki
    Abstract:

    We examined the hydrolysis mechanism of salicylic acid-tyrosine (salicyl-tyrosine) and salicylic acid-methionine conjugate (salicyl-methionine) in rabbits by exploring their behavior following intraduodenal and intracecal administration (72 and 36 mumol/kg, respectively: salicylic acid equivalent). A large amount of salicyl-methionine was absorbed following intraduodenal administration of salicyl-methionine, without being metabolized to salicylic acid in the small Intestinal mucosa. On the contrary, salicylic acid was detected in the blood following intraduodenal administration of salicyl-tyrosine, suggesting that salicyl-tyrosine was metabolized in the small Intestinal mucosa. After oral pretreatment of rabbits with kanamycin sulfate (6 x 400 mg) or tinidazole (6 x 160 mg), the hydrolysis of salicyl-tyrosine and salicyl-methionine following intracecal administration was inhibited significantly, indicating that the Intestinal Microorganisms were responsible for the biotransformation of these prodrugs. Furthermore, in rabbits orally pretreated with both kanamycin sulfate and tinidazole, a significant inhibition of salicylic acid formation from salicyl-tyrosine and salicyl-methionine following intracecal administration was observed.

Junzo Nakamura - One of the best experts on this subject based on the ideXlab platform.

  • Pharmacokinetic Analysis of In Vivo Metabolism of Amino Acid or Dipeptide Conjugates of Salicylic Acid in Rabbit Intestinal Microorganisms
    2015
    Co-Authors: Koyo Nishida, Hitoshi Sasaki, Mitsuhiko Kido, Junzo Nakamura
    Abstract:

    We analyzed the pharmacokinetics of salicylic acid (SA)-amino acid (alanine, glutamic acid, methionine and tyrosine) or-dipeptide (glycylglycine) conjugates in rabbits, by using a model that takes into account the metabolism of prodrug to SA by Intestinal Microorganisms, and also by model-independent analysis. The blood concentration profiles of these prodrugs and released SA following intracecal and oral administration to rabbits were obtained previously (Nakamura et al., J. Pharm. Pharmacol., 44, 295-299

  • Pharmacokinetic Analysis of In Vivo Metabolism of Amino Acid or Dipeptide Conjugates of Salicylic Acid in Rabbit Intestinal Microorganisms
    Pharmaceutical research, 1994
    Co-Authors: Koyo Nishida, Hitoshi Sasaki, Mitsuhiko Kido, Junzo Nakamura
    Abstract:

    We analyzed the pharmacokinetics of salicylic acid (SA)-amino acid (alanine, glutamic acid, methionine and tyrosine) or -dipeptide (glycylglycine) conjugates in rabbits, by using a model that takes into account the metabolism of prodrug to SA by Intestinal Microorganisms, and also by model-independent analysis. The blood concentration profiles of these prodrugs and released SA following intracecal and oral administration to rabbits were obtained previously (Nakamura et al., J. Pharm. Pharmacol., 44, 295-299, 1992; Chem. Pharm. Bull., 40, 2164-2168, 1992; Int. J. Pharm., 87, 59-66, 1992; J. Pharm. Pharmacol., 44, 713-716, 1992). First, the overall in vivo behaviour was evaluated by statistical moment analysis. Next, the blood concentration profiles of prodrug and SA following intracecal and oral administration were simultaneously fitted to the above model. In general, good agreement was observed between fitted lines and experimental data for every prodrug, suggesting the validity of this model. The obtained parameters characterized the difference in the rate of metabolism and absorption among the prodrugs. Lower absorbability and enhanced hydrolysis rate of the prodrug lead to prolonged blood concentration of SA.

  • A novel prodrug of salicylic acid, salicylic acid-glycylglycine conjugate, utilizing the hydrolysis in rabbit Intestinal Microorganisms.
    Journal of Pharmacy and Pharmacology, 1992
    Co-Authors: Junzo Nakamura, Koyo Nishida, Kumiko Asai, Hitoshi Sasaki
    Abstract:

    The hydrolysis of salicylic acid-glycylglycine conjugate (salicyl-glycylglycine) following oral, intravenous, intracaecal and rectal administration (434, 72, 36 and 36 mumol kg-1, respectively: equivalent to salicylic acid) was examined in rabbits to develop a novel prodrug of salicylic acid. Salicylic acid was detected in the blood 2 h after oral administration of salicyl-glycylglycine and it reached a maximum level (55.6 micrograms mL-1) at 15 h, whereas a small amount of salicyl-glycylglycine was found in the blood. In contrast, unchanged salicyl-glycylglycine was found mainly in the blood following its intravenous administration, suggesting the involvement of presystemic deconjugation in the hydrolysis of salicyl-glycylglycine. Immediate and very extensive salicyclic acid formation in the caecum was observed following intracaecal administration of salicyl-glycylglycine, suggesting that the Intestinal Microorganisms were responsible for the biotransformation of this compound. In-vitro incubation of salicyl-glycylglycine with caecal content showed that salicyl-glycylglycine was hydrolysed efficiently in the caecum. Consequently, the blood concentration of salicylic acid was prolonged extensively following rectal administration of salicyl-glycylglycine, indicating the usefulness of salicyl-glycylglycine as a prodrug of salicylic acid.

  • Unequal hydrolysis of salicylic acid-D-alanine and salicylic acid-L-alanine conjugate in rabbit Intestinal Microorganisms.
    Chemical & Pharmaceutical Bulletin, 1992
    Co-Authors: Junzo Nakamura, Chieko Tagami, Koyo Nishida, Hitoshi Sasaki
    Abstract:

    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.

  • Effect of oral pretreatment with antibiotics on the hydrolysis of salicylic acid-tyrosine and salicylic acid-methionine prodrugs in rabbit Intestinal Microorganisms.
    Chemical & pharmaceutical bulletin, 1992
    Co-Authors: Junzo Nakamura, Koyo Nishida, Mitsuhiko Kido, Hitoshi Sasaki
    Abstract:

    We examined the hydrolysis mechanism of salicylic acid-tyrosine (salicyl-tyrosine) and salicylic acid-methionine conjugate (salicyl-methionine) in rabbits by exploring their behavior following intraduodenal and intracecal administration (72 and 36 mumol/kg, respectively: salicylic acid equivalent). A large amount of salicyl-methionine was absorbed following intraduodenal administration of salicyl-methionine, without being metabolized to salicylic acid in the small Intestinal mucosa. On the contrary, salicylic acid was detected in the blood following intraduodenal administration of salicyl-tyrosine, suggesting that salicyl-tyrosine was metabolized in the small Intestinal mucosa. After oral pretreatment of rabbits with kanamycin sulfate (6 x 400 mg) or tinidazole (6 x 160 mg), the hydrolysis of salicyl-tyrosine and salicyl-methionine following intracecal administration was inhibited significantly, indicating that the Intestinal Microorganisms were responsible for the biotransformation of these prodrugs. Furthermore, in rabbits orally pretreated with both kanamycin sulfate and tinidazole, a significant inhibition of salicylic acid formation from salicyl-tyrosine and salicyl-methionine following intracecal administration was observed.

Koyo Nishida - One of the best experts on this subject based on the ideXlab platform.

  • Pharmacokinetic Analysis of In Vivo Metabolism of Amino Acid or Dipeptide Conjugates of Salicylic Acid in Rabbit Intestinal Microorganisms
    2015
    Co-Authors: Koyo Nishida, Hitoshi Sasaki, Mitsuhiko Kido, Junzo Nakamura
    Abstract:

    We analyzed the pharmacokinetics of salicylic acid (SA)-amino acid (alanine, glutamic acid, methionine and tyrosine) or-dipeptide (glycylglycine) conjugates in rabbits, by using a model that takes into account the metabolism of prodrug to SA by Intestinal Microorganisms, and also by model-independent analysis. The blood concentration profiles of these prodrugs and released SA following intracecal and oral administration to rabbits were obtained previously (Nakamura et al., J. Pharm. Pharmacol., 44, 295-299

  • Pharmacokinetic Analysis of In Vivo Metabolism of Amino Acid or Dipeptide Conjugates of Salicylic Acid in Rabbit Intestinal Microorganisms
    Pharmaceutical research, 1994
    Co-Authors: Koyo Nishida, Hitoshi Sasaki, Mitsuhiko Kido, Junzo Nakamura
    Abstract:

    We analyzed the pharmacokinetics of salicylic acid (SA)-amino acid (alanine, glutamic acid, methionine and tyrosine) or -dipeptide (glycylglycine) conjugates in rabbits, by using a model that takes into account the metabolism of prodrug to SA by Intestinal Microorganisms, and also by model-independent analysis. The blood concentration profiles of these prodrugs and released SA following intracecal and oral administration to rabbits were obtained previously (Nakamura et al., J. Pharm. Pharmacol., 44, 295-299, 1992; Chem. Pharm. Bull., 40, 2164-2168, 1992; Int. J. Pharm., 87, 59-66, 1992; J. Pharm. Pharmacol., 44, 713-716, 1992). First, the overall in vivo behaviour was evaluated by statistical moment analysis. Next, the blood concentration profiles of prodrug and SA following intracecal and oral administration were simultaneously fitted to the above model. In general, good agreement was observed between fitted lines and experimental data for every prodrug, suggesting the validity of this model. The obtained parameters characterized the difference in the rate of metabolism and absorption among the prodrugs. Lower absorbability and enhanced hydrolysis rate of the prodrug lead to prolonged blood concentration of SA.

  • A novel prodrug of salicylic acid, salicylic acid-glycylglycine conjugate, utilizing the hydrolysis in rabbit Intestinal Microorganisms.
    Journal of Pharmacy and Pharmacology, 1992
    Co-Authors: Junzo Nakamura, Koyo Nishida, Kumiko Asai, Hitoshi Sasaki
    Abstract:

    The hydrolysis of salicylic acid-glycylglycine conjugate (salicyl-glycylglycine) following oral, intravenous, intracaecal and rectal administration (434, 72, 36 and 36 mumol kg-1, respectively: equivalent to salicylic acid) was examined in rabbits to develop a novel prodrug of salicylic acid. Salicylic acid was detected in the blood 2 h after oral administration of salicyl-glycylglycine and it reached a maximum level (55.6 micrograms mL-1) at 15 h, whereas a small amount of salicyl-glycylglycine was found in the blood. In contrast, unchanged salicyl-glycylglycine was found mainly in the blood following its intravenous administration, suggesting the involvement of presystemic deconjugation in the hydrolysis of salicyl-glycylglycine. Immediate and very extensive salicyclic acid formation in the caecum was observed following intracaecal administration of salicyl-glycylglycine, suggesting that the Intestinal Microorganisms were responsible for the biotransformation of this compound. In-vitro incubation of salicyl-glycylglycine with caecal content showed that salicyl-glycylglycine was hydrolysed efficiently in the caecum. Consequently, the blood concentration of salicylic acid was prolonged extensively following rectal administration of salicyl-glycylglycine, indicating the usefulness of salicyl-glycylglycine as a prodrug of salicylic acid.

  • Unequal hydrolysis of salicylic acid-D-alanine and salicylic acid-L-alanine conjugate in rabbit Intestinal Microorganisms.
    Chemical & Pharmaceutical Bulletin, 1992
    Co-Authors: Junzo Nakamura, Chieko Tagami, Koyo Nishida, Hitoshi Sasaki
    Abstract:

    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.

  • Effect of oral pretreatment with antibiotics on the hydrolysis of salicylic acid-tyrosine and salicylic acid-methionine prodrugs in rabbit Intestinal Microorganisms.
    Chemical & pharmaceutical bulletin, 1992
    Co-Authors: Junzo Nakamura, Koyo Nishida, Mitsuhiko Kido, Hitoshi Sasaki
    Abstract:

    We examined the hydrolysis mechanism of salicylic acid-tyrosine (salicyl-tyrosine) and salicylic acid-methionine conjugate (salicyl-methionine) in rabbits by exploring their behavior following intraduodenal and intracecal administration (72 and 36 mumol/kg, respectively: salicylic acid equivalent). A large amount of salicyl-methionine was absorbed following intraduodenal administration of salicyl-methionine, without being metabolized to salicylic acid in the small Intestinal mucosa. On the contrary, salicylic acid was detected in the blood following intraduodenal administration of salicyl-tyrosine, suggesting that salicyl-tyrosine was metabolized in the small Intestinal mucosa. After oral pretreatment of rabbits with kanamycin sulfate (6 x 400 mg) or tinidazole (6 x 160 mg), the hydrolysis of salicyl-tyrosine and salicyl-methionine following intracecal administration was inhibited significantly, indicating that the Intestinal Microorganisms were responsible for the biotransformation of these prodrugs. Furthermore, in rabbits orally pretreated with both kanamycin sulfate and tinidazole, a significant inhibition of salicylic acid formation from salicyl-tyrosine and salicyl-methionine following intracecal administration was observed.

Mitsuhiko Kido - One of the best experts on this subject based on the ideXlab platform.

Jeffrey A. Mertens - One of the best experts on this subject based on the ideXlab platform.