Intrinsic factors are central to the growing fields of pharmacogenetics , pharmacogenomics , and personalized medicine.
Genetic polymorphisms i. In addition, there can be genetic differences in the diseases themselves e. In contrast to genetic intrinsic factors, physiological and pathological intrinsic factors are not dictated by DNA but are still individual-level characteristics leading to differences in drug response that are not environmentally driven.
While intrinsic factors act from within an individual, extrinsic factors wield their influence from the outside i. Extrinsic factors as a category can be rather broad, although drug developers tend to be most concerned with a subset that includes diet, concomitant medication use, and smoking habits.
Grapefruit juice is a well-known example of a food that can affect drug PK. In addition, because patients often suffer from more than one disease, they may be taking concomitant medications to treat multiple diseases. This is important because of potential drug-drug interactions , including impacts on drug exposure, safety, and effectiveness. This not only applies to prescription drugs, but also if a patient is taking an over-the-counter OTC drug e. For example, some compounds in tobacco smoke are potent inducers of drug metabolizing enzymes and can therefore increase the metabolism of certain drugs including caffeine.
Smoking can also affect how well drugs work and can increase safety risks. So, is there a way to predict whether your drug is likely to be affected? The International Council for Harmonisation ICH E5 guidelines summarize a number of properties that make a drug more likely to be sensitive to the influence of intrinsic and extrinsic factors.
These include drugs that exhibit:. The most palpable information for any drug is how the patient responds to treatment. This includes both the desirable and undesirable effects that a drug may cause. How patients respond to various drug doses is captured in the PK and the exposure-response relationship for a specific drug.
For most drugs, there is marked inter-individual variability in drug exposure following drug administration that can be related to intrinsic and extrinsic factors. This includes not only variability in the maximum concentrations observed i. This means that when the same dosing regimen is given to numerous people within the population, some may have low concentrations and be less likely to respond while others may have high concentrations and may be more likely to have an adverse event.
As with PK, relationships between concentrations in the blood and PD response i. One of the main objectives of toxicological studies is to establish dose-effect relations , to determine dose thresholds below which no health effect is to be feared. Traditionally , these doses are expressed in mass or number for fibers.
In the case of nanoparticles, it appears that the surface area is an important parameter of toxicity, which could justify that the dose be expressed in units of surface. Context Objectives Audience interactions How to use this website? Conception "A la carte" CEA training session. Reactivity Behaviour Production and methods.
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