Pharmacokinetics drug-related factor

The issues related to pharmacokinetics - drug absorption, distribution, metabolism, excretion - have always been important to the success of the drug discovery process. In many cases, not enough attention was paid to these factors in the early stages of the discovery... 

Before considering the pharmacology of any particular class of drugs, it is important to understand the basic underlying principles of drug action. The following two chapters in this section will deal with an important subject traditionally covered in the area of pharmacology known as pharmacokinetics (i.e., time-related factors such... 

It seeks to explain variability by identifying factors of demographic, pathophysiological, environmental, or drug-related origin that may influence the pharmacokinetic behavior of a drug. 

As shown in Figure 15.1, variations in the ethnic response to drugs are related to many interlinking factors. Genetic factors that control both pharmacokinetics and... 

The most useful pharmacokinetic variable for describing the quantitative aspects of all processes influencing the absorption (fa) and first-pass metabolism and excretion (Eg and Eh) in the gut and liver is the absolute bioavailability (F) [40]. This pharmacokinetic parameter is used to illustrate the fraction of the dose that reaches the systemic circulation, and relate it to pharmacological and safety effects for oral pharmaceutical products in various clinical situations. The bioavailability is dependent on three major factors the fraction dose absorbed (fa) and the first-pass extraction of the drug in the gut wall (EG) and/or the liver (EH) (Eq. (1)) [2-4, 15, 35] ... 

Pharmacokinetic principles, in addition to clinical factors such as the state of the patient, are utilized in determining dosage regimens. Factors that relate to the safety and efficacy of the drug, such as activity-toxicity relationships (therapeutic window and side effects), and pharmaceutical factors, such as dosage form and route of administration, must be considered.16... 

The 1996 Food Quality Protection Act (FQPA) now requires that an additional safety factor of 10 be used in the risk assessment of pesticides to ensure the safety of infants and children, unless the EPA can show that an adequate margin of safety is assured with out it (Scheuplein, 2000). The rational behind this additional safety factor is that infants and children have different dietary consumption patterns than adults and infants, and children are more susceptible to toxicants than adults. We do know from pharmacokinetics studies with various human pharmaceuticals that drug elimination is slower in infants up to 6 months of age than in adults, and therefore the potential exists for greater tissue concentrations and vulnerability for neonatal and postnatal effects. Based on these observations, the US EPA supports a default safety factor greater or less than 10, which may be used on the basis of reliable data. However, there are few scientific data from humans or animals that permit comparisons of sensitivities of children and adults, but there are some examples, such as lead, where children are the more sensitive population. It some cases qualitative differences in age-related susceptibility are small beyond 6 months of age, and quantitative differences in toxicity between children and adults can sometimes be less than a factor of 2 or 3. 

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