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QSAR World []
QSAR World []
A basic online course courtesy of Dr. David W. A. Bourne, OU College of Pharmacy []
*[ A basic online course courtesy of Dr. David W. A. Bourne, OU College of Pharmacy ]
*[ Pharmacokinetic software]
*[ Biokinetica Program]
Computer program package for analyzing pharmacokinetic data. []
E-book online as pdf file by Dr. T. Grabowski, []

Revision as of 20:31, September 13, 2007

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Pharmacokinetics (in Greek: "pharmacon" meaning drug and "kinetikos" meaning putting in motion, the study of time dependency) is a branch of pharmacology dedicated to the determination of the fate of substances administered externally to a living organism. In practice, this discipline is applied mainly to drug substances, though in principle it concerns itself with all manner of compounds ingested or otherwise delivered externally to an organism, such as nutrients, metabolites, hormones, toxins, etc. Pharmacokinetics is often divided into several areas including, but not limited to, the extent and rate of Absorption, Distribution, Metabolism and Excretion. This sometimes is referred to as the ADME scheme.

Absorption is the process of a substance entering the body. Distribution is the dispersion or dissemination of substances throughout the fluids and tissues of the body. Metabolism is the irreversible transformation of substances and its daughter metabolites. Excretion is the elimination of the substances from the body. In rare cases, some drugs irreversibly accumulate in a tissue in the body.

Pharmacokinetics is often studied in conjunction with pharmacodynamics. So while pharmacodynamics explores what a drug does to the body, pharmacokinetics explores what the body does to the drug.

Pharmacokinetics is sometimes abbreviated as "PK".

Pharmacokinetic Analysis

Pharmacokinetic analysis is performed by noncompartmental (model independent) or compartmental methods. Noncompartmental methods estimate the exposure to a drug by estimating the area under the curve of a concentration-time graph. Compartmental methods estimate the concentration-time graph using kinetic models.

Noncompartmental PK Analysis

Noncompartmental PK analysis is highly dependent on estimation of total drug exposure. Total drug exposure is most often estimated by Area Under the Curve methods, with the Trapezoidal Rule the most common area estimation method. Due to the dependence of the length of 'x' in the trapezoidal rule, the area estimation is highly dependent on the blood/plasma sampling schedule. That is, the closer your time points are, the closer the trapezoids are to the actual shape of the concentration-time curve.

Compartmental PK Analysis

Compartmental PK analysis uses kinetic models to describe and predict the concentration-time curve. PK compartmental models are often similar to kinetic models used in other scientific disciplines such as chemical kinetics and thermodynamics. The advantage of compartmental to noncompartmental analysis is the ability to predict the concentration at any time. The disadvantage is the difficulty in developing and validating the proper model. The simplest PK compartmental model is the one-compartmental PK model with IV bolus administration and first-order elimination.

Bioanalytical Methods

Bioanalytical methods are necessary to construct a concentration-time profile. Chemical techniques are employed to measure the concentration of drugs in biological matrix, most often plasma. Proper bioanalytical methods should be selective and sensitive.

Mass Spectrometry

Pharmacokinetics is often studied using mass spectrometry because of the complex nature of the matrix (often blood or urine) and the need for high sensitivity to observe low dose and long time point data. The most common instrumentation used in this application is LC-MS with a triple quadrupole mass spectrometer. Tandem mass spectrometry is usually employed for added specificity. Standard curves and internal standards are used for quantitation of usually a single pharmaceutical in the samples. The samples represent different time points as a pharmaceutical is administered and then metabolized or cleared from the body. Blank or t=0 samples taken before administration are important in determining background and insuring data integrity with such complex sample matrices. Much attention is paid to the linearity of the standard curve; however it is not uncommon to use curve fitting with more complex functions such as quadratics since the response of most mass spectrometers is less than linear across large concentration ranges.[1][2][3]

There is currently considerable interest in the use of very high sensitivity mass spectrometry for microdosing studies, which are seen as a promising alternative to animal experimentation.

See also

External Links

QSAR World [1]


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