There is an increasing concern over the rising incidence and prevalence of allergic diseases. Today’s allergies appear to be more persistent, more complex, and more severe than they used to be. They also pose greater diagnostic and management challenges to physicians. Allergic rhinitis is recognized as a global health problem that affects 30% of adults and 40% of children. Chronic idiopathic urticaria can be extremely debilitating and can greatly reduce a patient’s quality of life. Anaphylaxis is a life-threatening serious systemic allergic reaction, which can sometimes strike without warning. The main aim of this special issue of Drug Metabolism Reviews is to focus on drug metabolism/pharmacokinetic as well as pharmacodynamic aspects of drugs used in the treatment of allergic diseases. However, important concepts and new approaches, which should be known to physicians undergoing specialist training studies in allergy, will be discussed, even if specific examples referring to drugs used in the treatment of allergic diseases are still lacking. From each chapter, a conclusion will extract the major scientific and clinical message.
When a drug or xenobiotic is administered orally to an individual, the responses of the recipient can be thought of simply as a train of events that begins when the drug enters the bloodstream and ceases when the drug and its metabolites are completely eliminated from the body (with the exception of “hit and run” drugs, which produce an irreversible effect that persists after the elimination of the drug and its metabolites). Initially, there is a gradual rise in the blood level of the drug, which reaches a peak after a single dose—or a plateau after repeated doses—and if no more drug is administered, the level of the drug steadily declines until it is entirely eliminated. As time after dosage passes, several mechanisms that affect the disposition of the drug in the recipient come into play: it moves back and forth between the bloodstream and fluids and tissues; it may be sequestered by certain tissues; it may be biotransformed if it comes in contact with drug-metabolizing enzymes of the liver or other tissues; and a portion of the dose binds to receptors on the surface or within the cytoplasm of cells, resulting in the characteristic response of the drug.
Before coming to drug metabolism/pharmacokinetic considerations, we have outlined, in the first chapter of this special issue, the basic principles of the treatment of allergic diseases and considered the desirable and undesirable characteristics of the drugs used in the treatment of allergic diseases. The following two chapters concentrate on the basic pharmacokinetics and metabolism of drugs used in the treatment of allergic diseases and how this knowledge may be extended into physiologically based pharmacokinetics. Interindividual variability in pharmacokinetics is then considered, focusing on gender, genetic polymorphisms, and the effect of environmental factors, followed by considerations on the presence of comorbid diseases, age, pregnancy, and ethnicity. The review then moves into relatively new territory by considering the relationships between the plasma pharmacokinetics and the pharmacodynamic/therapeutic effects, particularly the calculation of the receptor occupancy in vivo and how this may be used to predict clinical efficacy. The final two chapters examine population-based analyses of drugs used for the treatment of allergic diseases and their possible interactions with food and other drugs.
We believe that this special issue will help allergologists, allergologists in training, and general practitioners in understanding what is relevant in the pharmacokinetic profile of a drug for the management of the allergic diseases and, consequently, how to use these drugs most effectively.