Influence of Gut Microflora on Bioavailability

Boxenbaum, Harold; Bekersky, Ihor; Jack, M.L.; Kaplan, Stanley A.

doi:10.3109/03602537908993894

Cited by 45 publications

(9 citation statements)

References 21 publications

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“…Many studies have pointed to the importance of intestinal micro-organisms in metabolizing a wide variety of drugs and other foreign compounds (Scheline 1968(Scheline , 1973Williams 1972;Boxenbaum et al 1974Boxenbaum et al ,1979Goldman 1978;Rowland 1986). In the previous report (Shibasaki et al 1985), we demonstrated the conversion of orally administered salicyluric acid to salicylic acid by gut microflora after oral administration in rabbits.…”

Section: Resultsmentioning

confidence: 99%

Decrease of Gastrointestinal Mucosal Damage by Salicyluric Acid Compared with Salicylic Acid in Rabbits

Nakamura

Katayama

Kido

et al. 1991

Journal of Pharmacy and Pharmacology

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The gastrointestinal mucosal damage following the oral administration of salicylic acid or salicyluric acid was examined in rabbits using a scanning electron microscope. Six and 24 h after treatment with salicylic acid, morphological changes of gastric mucosa were recognized. In rabbits treated with salicyluric acid, however, severe damage in the gastric mucosa was not found after 24 h compared with the treatment with salicylic acid. Following the treatment with salicylic acid, some mucosal damage in the duodenum, jejunum and ileum was observed after 24 h. The surface character of the duodenal, jejunal, ileal, caecal and colonic mucosa were almost identical compared with the control following the treatment with salicyluric acid. It was reported that salicyluric acid is metabolized to salicylic acid by the intestinal microorganisms. From these results, it was suggested that prodrugs utilizing the metabolism of salicyluric acid to salicylic acid by intestinal microorganisms may be useful in reducing gastrointestinal mucosal damage.

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Section: Resultsmentioning

confidence: 99%

Decrease of Gastrointestinal Mucosal Damage by Salicyluric Acid Compared with Salicylic Acid in Rabbits

Nakamura

Katayama

Kido

et al. 1991

Journal of Pharmacy and Pharmacology

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“…The significance of intestinal microorganisms to pharmacokinetics and pharmacology has been emphasized with respect to their ability to metabolize drugs and foreign compounds. The hydrolysis of glycine conjugates by intestinal microorganisms is well documented in various species (Norman & Grubb 1955;Hiilsmann & Statius van Eps 1967;Boxenbaum et al 1974Boxenbaum et al , 1979. In previous reports, we demonstrated that the glycine conjugate of salicylic acid (salicyluric acid) was metabolized to salicylic acid by intestinal microorganisms existing mainly in caecum and colon in rabbits (Shibasaki et al 1985;Nakamura et al 1986Nakamura et al , 1988a, rats (Nakamura et a1 1988b) and dogs (Nakamura et al 1989a).…”

mentioning

confidence: 82%

Development of a Prodrug of Salicylic Acid, Salicylic Acid-l-alanine Conjugate, Utilizing Hydrolysis by Rabbit Intestinal Microorganisms

Nakamura

Tagami

Nishida

et al. 1992

Journal of Pharmacy and Pharmacology

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The hydrolysis of salicylic acid-L-alanine conjugate (salicyl-L-alanine) following oral, intravenous, intracaecal and rectal administration (60, 10, 5 and 5 mg kg-1, respectively: salicylic acid equivalent) was examined in rabbits. Salicylic acid was detected in the blood 2 h after oral administration of salicyl-L-alanine and reached a maximum concentration at 10 h, whereas salicyl-L-alanine was rapidly eliminated. In contrast, unchanged salicyl-L-alanine only was found following intravenous administration of salicyl-L-alanine, suggesting that presystemic de-conjugation of salicyl-L-alanine was involved. The intestinal mucosal de-conjugation of salicyl-L-alanine was not recognized in the in-situ intestinal sac preparation with complete mesenteric venous blood collection. Immediate and very extensive salicylic acid formation in the caecum was found following intracaecal administration of salicyl-L-alanine. After oral pretreatment of rabbits with kanamycin sulphate, a significant inhibition of salicylic acid formation following intracaecal administration of salicyl-L-alanine was observed, indicating that the intestinal microorganisms were responsible for the biotransformation of salicyl-L-alanine. In-vitro incubation of salicyl-L-alanine with gut contents showed that the major source of its hydrolysis was the hind gut. Consequently, the blood concentration of salicylic acid was prolonged extensively following rectal administration of salicyl-L-alanine, suggesting the usefulness of salicyl-L-alanine as a prodrug of salicylic acid.

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“…The role of the gut microbiota in modulating the response of humans and animals to drugs was once an active field of research (e.g., see [3][4][5][6][7][8][9]) but this topic has been somewhat neglected in recent years, by both academia and the pharmaceutical industry, though interestingly not by food scientists and those interested in the effects of pharmacologically-active dietary constituents. However, for the drug metabolism community it is arguable that the gut microbiota of animals and man represents a largely forgotten organ of drug metabolism and disposition.…”

Section: Introductionmentioning

confidence: 99%

The Role of Gut Microbiota in Drug Response

Wilson¹,

Nicholson²

2009

CPD

103

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Higher organisms such as mammals exist in a symbiotic relationship with their gut microbiota, formed from a diverse and highly metabolically active consortium of species. The gut microbiota, in addition to their ability to process dietary derived material, are also capable of performing a range of biotransformations on xenobiotics, such as drugs and their metabolites, in ways that can affect absorption and bioavailability. The potential for the gut microflora to influence drug metabolism and toxicity in unexpected ways is discussed.

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Influence of Gut Microflora on Bioavailability

Cited by 45 publications

References 21 publications

Decrease of Gastrointestinal Mucosal Damage by Salicyluric Acid Compared with Salicylic Acid in Rabbits

Decrease of Gastrointestinal Mucosal Damage by Salicyluric Acid Compared with Salicylic Acid in Rabbits

Development of a Prodrug of Salicylic Acid, Salicylic Acid-l-alanine Conjugate, Utilizing Hydrolysis by Rabbit Intestinal Microorganisms

The Role of Gut Microbiota in Drug Response

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