Food-effect studies design

In general, however, it is recommended to perform specific well-designed food-effect studies with adequate power for large differences to capture meaningful deviations in exposure. 

In conclusion, phytic acid forms soluble complexes with Ca2+ at intestinal pH under a variety of conditions and fails to inhibit Ca2 bioavailability to mice in our experimental system. Despite the hazard in direct extrapolation of results obtained with animals kept on a well-defined dietary regimen to humans consuming a complex diet, many elements of which affect Ca2+ bioavailability, our data demonstrate the need for a reevaluation of the putative antinutritional properties of dietary phytate. Our further contention that adequate levels of dietary phytate may actually be beneficial due to its food preserving properties and its protection against colonic cancer will warrant a prospective epidemiological human study designed to assess the longterm effects of dietary phytate on mineral bioavailability and inflammatory bowel diseases. 

It should be noted that in both guidances BCS-based biowaivers do not apply to food effect BA studies or pharmacokinetic studies other than those designed to test for BE. 

The developmental studies are intended to provide information on any adverse effects of the food additive on pregnant women and their developing concepms. The study designs used are identical to those used to assess the prenatal toxicity of chemicals, except that dietary administration is preferred over gavage dosing. 

Human perception of flavor occurs from the combined sensory responses elicited by the proteins, lipids, carbohydrates, and Maillard reaction products in the food. Proteins Chapters 6, 10, 11, 12) and their constituents and sugars Chapter 12) are the primary effects of taste, whereas the lipids Chapters 5, 9) and Maillard products Chapter 4) effect primarily the sense of smell (olfaction). Therefore, when studying a particular food or when designing a new food, it is important to understand the structure-activity relationship of all the variables in the food. To this end, several powerful multivariate statistical techniques have been developed such as factor analysis Chapter 6) and partial least squares regression analysis Chapter 7), to relate a set of independent or "causative" variables to a set of dependent or "effect" variables. Statistical results obtained via these methods are valuable, since they will permit the food... 

Some strategies have been put in place to mitigate or minimize the risks that arise from such unmanageable food effects for Compound A. An extensive population pharmacokinetic-pharmacodynamic program had been designed for Phases ll/lll studies of Compound A a number of... 

The study protocol must, first and foremost, contain a clearly stated objective of the research activity to follow. It has not been unusual for studies to be conducted without all of the study team understanding the scope of the Investigation. For example, a study conducted to determine the Identity and relative quantity of a pesticide and Its metabolites 1n the edible portions of food-producing animals should be restricted to the activities necessary to provide this Information. Without a clearly stated objective, this type of study could Instead be manipulated Into an attempt to determine toxicological responses or pathological effects. The data obtained could be of questionable value because the protocol design would not contain the necessary elements to provide reliable data. This 1s not to say that combined studies are of no value, but 1f a study 1s multidisciplinary 1n nature, the study design should contain Input from staff qualified 1n the disciplines Involved. 

Experience has shown that the exploratory profiling of the impact of gender, high age, and food intake (in the form of a food screen for worst case food effects) on drug disposition (pharmacokinetics) and safety can be conveniently done in one study with the design described in this article. If a notable effect of these parameters is/are seen, then confirmatory studies need to be performed. 

This type of hADME study will always have an explorative character, and typically comprises less than the normal minimum of 12 subjects for a PK study. If the compound is expected to show different and unpredictable ADME characteristics in special populations, then it might be necessary to include these populations in addition to normal, healthy subjects. Or, if other conditions might influence ADME in an unpredictable manner (e.g. food effects), then it might even be necessary to run the study in a cross-over design. The inclusion of females (being not of childbearing potential) was discussed several times, but it seems to be a rare exception for hADME studies. 

Food-effect bioavailability and fed bioequivalence studies Study design, data analysis, and labeling. In Draft Guidance for Industry, U.S. Department of Health and Human Services, Food and Drug Administration, October, 2001. 

Extensive animal feeding studies designed to detect the potential presence of toxic substances in various irradiated foods have been carried out since the 1950s, mostly in USA and Europe. None of the studies carried out under the auspices of the IFIP (24 involved countries, 67 technical reports published in 12 years) showed any indication that the irradiated foods contained radiation-produced carcinogens or other toxic substances. In a French study, for example, nine chemical compounds that had been identified in irradiated starch were fed daily to rats in amounts calculated to be 800 times the amounts the animals might be expected to consume from a normal daily intake of irradiated starch. No toxic effect was found even at this exaggerated rate of intake (chapter 8 of [1 ]). 

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