SwePub - search: WFRF:(Basit Abdul W.)

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1.	Sousa, Tiago, et al. (author) The gastrointestinal microbiota as a site for the biotransformation of drugs 2008 In: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 363:1-2, s. 1-25 Journal article (peer-reviewed)abstract There are 100 trillion microbes in the human gastrointestinal tract with numbers increasing distally. These microbiota secrete a diverse array of enzymes (primarily for carbohydrate and protein fermentation) giving them substantial metabolic potential which can have major implications for drug stability. At least thirty drugs which are, or have been, available commercially, were subsequently shown to be substrates for these bacterial enzymes, and with increasing numbers of new and existing drugs having the potential for contact with the distal gut (through modified release systems or poor solubility/permeability), many more are expected to be discovered. The major concern with bacterial drug degradation is the behaviour of the metabolite; is it more or less active than the parent compound, or has toxicity resulted? For example, there were eighteen deaths in 1993 due to a drug interaction in which a toxic drug metabolite was produced by bacterial fermentation. Thus, the objective of this review is the provision of a comprehensive overview of this area; the gastrointestinal microbiota, their drug substrates and metabolic mechanisms, and approaches to studying this further are discussed.

Sousa, Tiago, et al. (author)
The gastrointestinal microbiota as a site for the biotransformation of drugs
2008
In: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 363:1-2, s. 1-25
Journal article (peer-reviewed)abstract
- There are 100 trillion microbes in the human gastrointestinal tract with numbers increasing distally. These microbiota secrete a diverse array of enzymes (primarily for carbohydrate and protein fermentation) giving them substantial metabolic potential which can have major implications for drug stability. At least thirty drugs which are, or have been, available commercially, were subsequently shown to be substrates for these bacterial enzymes, and with increasing numbers of new and existing drugs having the potential for contact with the distal gut (through modified release systems or poor solubility/permeability), many more are expected to be discovered. The major concern with bacterial drug degradation is the behaviour of the metabolite; is it more or less active than the parent compound, or has toxicity resulted? For example, there were eighteen deaths in 1993 due to a drug interaction in which a toxic drug metabolite was produced by bacterial fermentation. Thus, the objective of this review is the provision of a comprehensive overview of this area; the gastrointestinal microbiota, their drug substrates and metabolic mechanisms, and approaches to studying this further are discussed.

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