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Dietary Supplements A Framework for Evaluating Safety (2005) / Chapter Skim
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8 Interactions
Pages 235-246

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From page 235...
... will result in adverse clinical outcomes due to an increase or decrease in the level of the dietary supplement in the organism, an increase or decrease in the level of other xenobiotics,2 or combined toxicities. Potential adverse clinical outcomes may result if a dietary supplement lowers a drug's effective concentration.
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From page 236...
... Other examples include cholestyramine, which adsorbs other drugs, thereby decreasing their availability for absorption, and antacids, which can block iron or zinc uptake. In addition to forming complexes, antacids may significantly change the rate of absorption of other chemicals by altering gastric pH or gastric emptying time, depending on the extent to which pH affects the amount of chemical in the un-ionized state (Azarnoff and Hurwitz, 1970; Hurwitz, 1971, 1977; Hurwitz and Scholzman, 1974; Hurwitz and Sheehan, 1971; Hurwitz et al., 1976)
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From page 237...
... For example, two substances may each affect the same organ, but in different ways, and when taken together may greatly increase the propensity for organ damage, even if toxic effects are not detected independently. Interactions with Dietary Supplements There are examples of pharmacodynamic interactions that have been noted with dietary supplement ingredients.
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From page 238...
... These interactions include effects caused by the chemicals on xenobiotic metabolizing enzymes and transporters that affect the time course of the concentration of one or both of the chemicals in the body. These interactions commonly take place in the intestines, liver, or kidney and are further categorized based on their site of action.
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From page 239...
... . Due to differences in human and animal transporters, the methods often employ human transporter proteins expressed in artificial in vitro systems, enabling the detailed study of human transporter protein functions with regard to drugs and other xenobiotic substances, including dietary supplement ingredients.
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From page 240...
... PREDICTING THE POTENTIAL OF INGREDIENTS TO CAUSE PHARMACOKINETIC INTERACTIONS Techniques currently available allow the determination of the extent to which one substance may impact the concentration of other concomitantly ingested substances. There are numerous well-accepted in vitro assays designed specifically to determine if a drug may interact with other substances.
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From page 241...
... Whether an interaction predicted on the basis of in vitro studies actually occurs clinically will depend on whether the dietary supplement compound attains a concentration in vivo adequate to reproduce the effect observed in vitro, as discussed in more detail below. In Vitro Prediction of Pharmacokinetic Effects In vitro studies for determining which xenobiotics affect transporters and metabolic enzymes ideally employ human transporter proteins or human metabolic enzymes.
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From page 242...
... Numerous other polymorphisms in xenobiotic metabolism have been or are being identified. Such data can serve to identify people who may be particularly sensitive to dietary supplements cleared by these polymorphic xenobiotic metabolizing systems.
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From page 243...
... A number of pieces of information can suggest a possible interaction between a dietary supplement ingredient and other substances. The potential seriousness of these interactions varies and is placed in perspective by considering if a particular interaction leads to serious adverse events and the likelihood that the interaction will occur.
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From page 244...
... 1993. Oral yohimbine increases blood pressure and sympathetic nervous outflow in hypertensive patients.
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From page 245...
... 2002. Sensitization of human neutrophil defense activities through activation of platelet-activating factor receptors by ginkgolide B, a bioactive component of the Ginkgo biloba extract EGB 761.
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From page 246...
... 1975. Diphenylhydantoin potency and plasma protein binding.
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Key Terms

  • dietary supplements
  • protein binding
  • pharmacodynamic interactions
  • serious adverse
  • xenobiotic metabolizing

  • pharmacokinetic interactions
  • metabolizing enzymes
  • supplement ingredient
  • supplement ingredients
  • adverse event

  • drug metabolism
  • cyp enzymes
  • vitro studies
  • toxic effects
  • human transporter

  • plasma protein
  • vitro assays
  • human cytochrome
  • hawthorne leaf
  • drugs metabolized

  • indirect pharmacodynamic
  • exp ther
  • pharmacol ther
  • vitro information
  • binding sites

  • enzyme metabolism
  • indiana university
  • grapefruit juice
  • adverse clinical
  • human proteins


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