Pharmacokinetic interactions process

Interactions resulting from a change in the amount of diug reaching the site of action are called pharmacokinetic interactions (Fig. 1). A co-administered diug can affect any of the processes of absorption, distribution, metabolism, and excretion of the original diug, which are determinants of its pharmacokinetic profile [1-3]. 

Pharmacokinetic interactions may occur during one or more of the pharmacokinetic processes whereby the drug reaches its site of action and is then eliminated (i.e. absorption, distribution, metabolism and excretion). Such interactions may result in a change in the drug concentration at the site of action with subsequent toxicity or decreased efficacy. 

The scope of mechanisms causing pharmacokinetic interactions may include alterations in one or more of the absorption, distribution, metabolism, and elimination processes. The alterations may reflect effects of the developmental drug on the pharmacokinetics of the potential interaction partner, and vice versa. 

From a clinical point of view, adverse drug interactions (therapeutically undesirable effects) are particularly important. These interactions reduce or enhance the effects of a drug, causing emergence of toxic symptoms or pharmacological action qualitatively different from that expected. Undesirable interactions require specific control of therapy or even modification of doses, and are a result of a variety of mechanisms and the impact of the patient s individual characteristics on drug metabolism. Sometimes completely unfamiliar or unusual mechanisms underlie two types of reactions, positive or adverse. Most often, however, these reactions are nothing other than repeated, sometimes very well-known, pharmacokinetic processes (pharmacokinetic interactions), most of which are a result of inhibition or induction of metabolic enzymes. 

The broad definition of a drug as "any chemical that affects living processes" (Benet, Mitchell, and Sherner 1990a) is helpful in understanding the relationship between the body and administered medications. This is a fluid and interactive process, composed of two elements pharmacodynamics and pharmacokinetics. 

Pharmacokinetic interactions are those that can affect the processes by which drugs are absorbed, distributed, metabolised and excreted (the so-called ADME interactions). 

Finally, site-specific delivery also depends on the extent of competing processes in the biological system as well as the interaction of the drug itself with the biological system. Therefore successful design of polymeric drug delivery approaches requires a comprehensive appreciation of the pharmacology, pharmacokinetics, and pharmacodynamics involved. 

Apart from patient-specific parameters, external factors - most importantly the concomitant uptake of certain other chemicals present in diet, environment and especially other drugs - influence drug actions. Possible effects are manifold and can affect all stages of pharmacokinetic and pharmacodynamic processes in the body. Also direct interaction and inactivation of concomitantly administered substances are possible. Drug-drug interactions via modulation of metabolism present a very hot topic in pharmaceutical research and drug design. 

In a recent review of pharmacokinetics in drug discovery, Ruiz-Garcia et al. [81] compiled an exhaustive list of software resources for absorption prediction. The main topic in the described databases is transporters, in particular the ATP-binding cassette, of which the efflux transporter P-gp and the peptide transporter PEPTl are well known examples. These examples show that science is moving away from the simplistic passive transport view of permeability and towards an all-inclusive, mechanism-understanding model of absorption, which takes account of all the interactions between the agents involved in the specific permeation process. 

Heparinoid polysaccharides such as heparan sul te and heparin are able to interact with numerous proteins and influence vital biological processes. Heparinoid mimetics were prepared to reduce the structural complexity of heparinoids and to obtain selectivities. This artide summarizes the development of heparinoid mimetics of different classes including representative syntheses and biological activities. Largely simplified compounds with regard to structure and synthetic access are described which maintain or exceed the activity of heparinoid polysaccharides. One of the recipes to increase binding or modify pharmacokinetic parameters was the introduction of hydrophobic groups. 

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