Pharmacokinetics defined

Pharmacology and clinical pharmacology define the desirable and undesirable effects of drugs and xenobiotics whereas pharmacokinetics defines the various processes that are involved in absorption - distribution - elimination of these agents. Needless to say that the former may strongly influence the latter. 

The term virtual screening or in silica screening is defined as the selection of compounds by evaluating their desirability in a computational model [17]. The desirability comprises high potency, selectivity, appropriate pharmacokinetic properties, and favorable toxicology. 

Bioavailability, Bioequivalence, and Pharmacokinetics. Bioavailabihty can be defined as the amount and rate of absorption of a dmg into the body from an adrninistered dmg product. It is affected by the excipient ingredients in the product, the manufacturing technologies employed, and physical and chemical properties of the dmg itself, eg, particle size and polymorphic form. Two dmg products of the same type, eg, compressed tablets, that contain the same amount of the same dmg are pharmaceutical equivalents, but may have different degrees of bioavailabihty. These are chemical equivalents but are not necessarily bioequivalents. For two pharmaceutically equivalent dmg products to be bioequivalent, they must achieve the same plasma concentration in the same amount of time, ie, have equivalent bioavadabihties. 

Clinical Pharmacokinetics. Clinical pharmacokinetics attempts to define the relationship between dmg concentration and therapeutic response. The underlying assumption is that response is proportional to dmg concentration at the site of action. This concentration is dependent on many... 

Exposure should be by the practical route. Other conditions, such as number and magnitude of exposures, should kiclude at least one level representative of the practical situation monitoring should be appropriate to the needs for conducting the study and when practically and economically possible, pharmacokinetic observations should be undertaken ki order to better define the relationship of dose to metaboHc thresholds. 

X-ray crystallographic studies (59) have defined the conformations and hydrogen bonding of the tetracyclines under nonpolar and polar conditions. These are shown ia Figure 3. It is beheved that the equiUbrium between the 2witterionic and nonioni2ed forms is of importance for the broad-spectmm antibacterial activity, membrane permeation, and pharmacokinetic properties. 

A knowledge of physiology and pharmacokinetics is needed (Fanis et al. 1993 Monteiro and Furness 2001). Levels of mercuiy normally vary among internal tissues, and the time to equilibrate within each tissue varies. For example, blood mercury levels normally reflect veiy recent exposure, while brain and liver levels reflect longer-term exposure. Tissue-specific mechanisms of detoxification and seqnestration, among other processes, must be understood to define the bioactive moiety in observed tissue bmdens before a clear expression of toxicity can be derived (Woodetal. 1997). 

The pharmacokinetic parameters of the model are then readily derived from the defining equations and the results of the regression ... 

Interroute extrapolation. The values for pharmacokinetic variables in the Leggett Model are independent of the route of exposure. Based on the description of the inputs to the model provided by Leggett (1993), lead intake from different exposure routes is defined as a total lead intake from all routes of exposure. 

Thus, %F is defined as the area under the curve normalized for administered dose. Blood drug concentration is affected by the dynamics of dissolution, solubility, absorption, metabolism, distribution, and elimination. In addition to %F, other pharmacokinetic parameters are derived from the drug concentration versus time plots. These include the terms to describe the compound s absorption, distribution, metabolism and excretion, but they are dependent to some degree on the route of administration of the drug. For instance, if the drug is administered by the intravenous route it will undergo rapid distribution into the tissues, including those tissues that are responsible for its elimination. 

According to USP 28 [1], the range of an analytical method can be defined as the interval between upper and lower levels (in the Pharmaceutical Industry usually a range from 80 to 120% of the target concentrations tested) of the analyte that have been demonstrated to be determined with a acceptable level of precision, accuracy, and linearity. Routine analyses should be conducted in this permitted range. For pharmacokinetic measurements, a wide range should be tested, where the maximum value exceeds the highest expected body fluid concentration, and the minimum value is the QL. 

Solution equilibria for gadolinium imaging agents have been studied with consideration for pharmacokinetic, protein binding, elimination, and safety aspects of the dmgs. The thermodynamic stability constant, Kq defined by equation 7.4 must be large for clinically viable agents. Some Kq l data are listed in Table 7.3. 

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