Pharmacokinetic -toxicokinetic

Exposure Assessment. Single and multiple dose pharmacokinetics, toxicokinetics and tissue distribution studies in relevant species are useful. Proteins are not given orally demonstrating absorption and mass balance is not typically a primary consideration. Rather, this segment of the test should be designed to determine... 

Further refinements of methods require more elaborate models with explicit or implicit assumptions and defaults, e.g.. Physiologically Based Pharmacokinetic/Toxicokinetic (PBPK/PBTK) models, which may also provide modeled information on the target concentrations/amounts (Section 4.3.6). 

NAIVE average data Standard preclinical pharmacokinetics / toxicokinetics data Simplicity Misidentification of the structural model, poor parameter estimation, confounded variability... 

See also Biotransformation Distribution Excretion Exposure Gastrointestinai System Modifying Factors of Toxicity Pharmacokinetics/Toxicokinetics Respiratory Tract Skin Toxicity Testing, Dermai Toxicity Testing, Inhaiation. 

Epidemiology Mechanisms of Toxicity Medical Sun/eil-lance Molecular Toxicology-Recombinant DNA Technology Pharmacokinetic Models Pharmacokinetics/ Toxicokinetics Risk Assessment, Human Health. 

See also Carboxylesterases Glutathione Kidney Liver Pharmacokinetics/Toxicokinetics. 

See also Absorption Blood Developmental Toxicology Excretion Gastrointestinal System Kidney Liver Metal-lothionein Neurotoxicity Pharmacokinetics/Toxicokinet-ics Skeletal System. 

See also Benchmark Dose Exposure Assessment Exposure Criteria Hazard Identification Hormesis, LD50/ LC50 (Lethai Dosage 50/Lethai Concentration 50) Levels of Effect in Toxicoiogicai Assessment Maximum Allowable Concentration (MAC) Maximum Tolerated Dose (MTD) Pharmacokinetics/Toxicokinetics Reference Concentration (RfC) Reference Dose (RfD) Risk Assessment, Ecological Risk Assessment, Human Health Risk Characterization Toxicity, Acute. 

See also Absorption Biotransformation Distribution Kidney Liver Metais Pharmacokinetics/Toxicokinetics. 

See also Dose-Response Relationship Food and Drug Administration, US Investigative New Drug Application LD50/LC50 (Lethal Dosage 50/Lethal Concentration 50) Pharmacokinetics/Toxicokinetics Redbook. 

Pharmacokinetics/toxicokinetics is the area of toxicology that is concerned with the role of absorption, distribution, metabolism, and excretion of toxicants in the body. These events, some of which may be interdependent, often have a very significant impact on the toxicity of a chemical in a specific species. Quantitative characterization of the time profile of absorption, distribution, metabolism, and excretion of xenobiotic compounds is included in the area of pharmacokinetics. In this sense, pharmacokinetics is used synonymously with toxicokinetics. 

Pharmacokinetics/toxicokinetics may be defined as the study of the dynamic movements of xenobiotics during their passage through the body and as such encompass the concept of disposition described previously (Figure 1). In simpler words, it tells us what the body does to foreign chemicals. To that end, pharmacokinetic/toxicokinetic analysis uses mathematical terms, or equations, to describe the time course of the absorption and disposition of xenobiotics in the body and proposes simplified representations (models) of the relationship between time and movements of xenobiotics. Once the information on the concentration of a chemical in biologically relevant parts of the body is provided by pharmacokinetic/toxicokinetic studies, it then usually becomes possible to better understand, interpret, and even predict the nature and the extent of the biological effects of xenobiotics. 

The purpose of this article is to introduce the reader to simple basic concepts and principles of pharmacokinetic/toxicokinetic analysis using both types of models - compartmental and physiologically based. 

As seen earlier, exposure conditions amenable to pharmacokinetic/toxicokinetic analysis are such that the rate of the biological processes (e.g., diffusion across membranes, biotransformation, excretion by glomerular filtration, etc.) is proportional to the concentration or amount of a xenobiotic in a given compartment such as blood. The rate is then said to be governed by first-order kinetics (see Figures 2 and 3). 

Pharmacokinetic/toxicokinetic analysis is a very important tool that can help toxicologists understand how the body handles foreign chemicals. With a good knowledge of the time course relationship between exposure to chemicals and their concentration in various tissues and organs, toxicologists are in a position to better interpret and predict the nature and extent of toxicity. 

Pharmacokinetics/Toxicokinetics, Pages 383-390, Robert Tardif and Jules Brodeur SummaryPlus Full Text + Links PDF (120 K)... 

---