The role of the gastrointestinal microflora in the metabolism of drugs

Shamat, M.Abu

doi:10.1016/0378-5173(93)90121-u

Cited by 41 publications

(17 citation statements)

References 75 publications

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“…The vast majority of bacteria are found in the distal gut and counts have been estimated to be 10 11 per gram, compared to 10 4 per gram in the proximal small intestine [34][35][36]. Bacteria sensitivity of the HPMA copolymer 9-AC conjugate resulted in much higher concentrations of released 9-AC in the cecum contents, feces, cecal and colon tissues than that of oral free drug.…”

Section: Discussionmentioning

confidence: 99%

Biodistribution and pharmacokinetics of colon-specific HPMA copolymer–9-aminocamptothecin conjugate in mice

Gao

Lü

Kopečková

et al. 2007

Journal of Controlled Release

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A water soluble N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer -9-aminocamptothecin (9-AC) conjugate was designed for oral colon-specific drug delivery for the treatment of colon cancer. Comparative studies between the polymer conjugate and free drug have been performed to assess their biodistribution and pharmacokinetics in mice. After oral administration of equal doses of the polymer conjugate or free 9-AC, the drug concentrations in major organs at fixed time points were determined using an HPLC-fluorescence assay. Only 2±1% of 9-AC released from the polymer conjugate was detected in small intestine (SI), and the mean peak concentration of free 9-AC was 45-fold higher than that from released drug. Colon-specific release of 9-AC produced high local concentrations. The mean peak concentration of released 9-AC in cecal contents, feces, cecal tissue, and colon tissue were, respectively, 3.2-fold, 3.5-fold, 2.2-fold and 1.6-fold higher than that using free 9-AC. In plasma, the high and sharp drug concentration profile from free drug was in contrast to the relatively low and flat pharmacokinetic profile obtained from drug released from the HPMA copolymer. There was no significant difference between released and free drug for the area under the concentration-time curve (AUC) and bioavailability values. As a consequence of the colonspecific release of unmodified 9-AC from the polymer conjugate, antitumor efficacy can be anticipated to be enhanced due to prolonged colon tumor exposure to higher and more localized drug concentrations.

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Section: Discussionmentioning

confidence: 99%

Biodistribution and pharmacokinetics of colon-specific HPMA copolymer–9-aminocamptothecin conjugate in mice

Gao

Lü

Kopečková

et al. 2007

Journal of Controlled Release

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“…Furthermore, the majority of hepatic metabolic reactions comprise oxidation and conjugation, whereas the microflora tends mainly to catalyze reductive and hydrolytic reactions. Thus, the intestinal microflora represent a distinct and a potentially important site for metabolic transformation of xenobiotics including drugs and toxicants (Shamat, 1993). Human intestinal microbiota can have a major impact on drug or toxicant metabolism and ultimately on oral bioavailability of them.…”

Section: Toxicity Testings Of Bacteria Cultured Media With Arbutin Inmentioning

confidence: 99%

Role of metabolism by intestinal bacteria in arbutin-induced toxicity in vitro

Kang

Kim

et al. 2011

Arch. Pharm. Res.

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A possible role of metabolism by intestinal bacteria in arbutin-induced toxicity was investigated in mammalian cell cultures. Following an incubation of arbutin with intestinal bacteria, either Bifidobacterium longum HY81 or Bifidobacterium adolescentis, for 24 h, its aglycone hydroquinone could be produced and detected in the bacterial culture media. The bacterial growth was not affected up to 10 mM arbutin in the culture medium. When the toxicity of bacteria cultured medium with arbutin was tested in the HepG2 cell lines, the medium with arbutin was more toxic than either parent arbutin only or bacteria cultured medium without arbutin, indicating that metabolic activation might be required in arbutin-induced toxicity. In addition, bacteria cultured medium with arbutin could suppress LPS and ConA mitogenicity in splenocyte cultures prepared from normal mice. The results indicate that the present toxicity testing system might be applied for assessing the possible role of metabolism by intestinal bacteria in certain chemical-induced toxicity in mammalian cell cultures.

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“…Gut microbiota also affect the metabolism and toxicity of xenobiotics. They express a diverse array of bacterial enzymes which have the ability to metabolize drugs far more extensively than any other part of the body 13,14 . orally taken drugs reach the gastrointestinal tract and before being absorbed through the epithelial membrane into the blood they are exposed to the intestinal microbiota that may alter their disposition, efficacy and toxicity.…”

Section: Introductionmentioning

confidence: 99%

Human gut microbiota plays a role in the metabolism of drugs

Jourová¹,

Anzenbacher²,

Anzenbacherová³

2016

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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a Background and Aims. The gut microbiome, an aggregate genome of trillions of microorganisms residing in the human gastrointestinal tract, is now known to play a critical role in human health and predisposition to disease. It is also involved in the biotransformation of xenobiotics and several recent studies have shown that the gut microbiota can affect the pharmacokinetics of orally taken drugs with implications for their oral bioavailability. Methods. Review of Pubmed, Web of Science and Science Direct databases for the years 1957-2016. Results and Conclusions. Recent studies make it clear that the human gut microbiota can play a major role in the metabolism of xenobiotics and, the stability and oral bioavailability of drugs. Over the past 50 years, more than 30 drugs have been identified as a substrate for intestinal bacteria. Questions concerning the impact of the gut microbiota on drug metabolism, remain unanswered or only partially answered, namely (i) what are the molecular mechanisms and which bacterial species are involved? (ii) What is the impact of host genotype and environmental factors on the composition and function of the gut microbiota, (iii) To what extent is the composition of the intestinal microbiome stable, transmissible, and resilient to perturbation? (iv) Has past exposure to a given drug any impact on future microbial response, and, if so, for how long? Answering such questions should be an integral part of pharmaceutical research and personalised health care.

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The role of the gastrointestinal microflora in the metabolism of drugs

Cited by 41 publications

References 75 publications

Biodistribution and pharmacokinetics of colon-specific HPMA copolymer–9-aminocamptothecin conjugate in mice

Biodistribution and pharmacokinetics of colon-specific HPMA copolymer–9-aminocamptothecin conjugate in mice

Role of metabolism by intestinal bacteria in arbutin-induced toxicity in vitro

Human gut microbiota plays a role in the metabolism of drugs

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