Pharmacokinetic model describing the disposition

Dailey JW, Gupta PK, Hung CT. 1990. A physiological pharmacokinetic model describing the disposition of lead in the absence and presence of L-ascorbic acid in rats. Toxicol Lett 50 337-348. 

Leavens, T.L. Bond, J.A. (1996) Pharmacokinetic model describing the disposition of butadiene and styrene in mice. Toxicology, 113, 310-313... 

Figure 2. Hypothetical pharmacokinetic model describing the disposition of a parent chemical (P) and its metabolite (M) in the body. The parameters are described in the text.

A pharmacokinetic model for the disposition of chlordiazepoxide HC1 in the dog has been presented in terms of a six-compartment open system16. The excellent agreement between the simulated and experimental data reflects the reliability of the assumption of first-order kinetics for all processes. The model provides a basis for the elucidation and quantitation of chlordiazepoxide and its pharmacologically active biotransformation products, the N-desmethyl metabolite and the lactam. The pathways in man17-19 have been shown to be similar to those in the dog to the extent to which they are described in the model. 

The group of Byron and co-workers established an IPL model specifically to study drug deposition and absorption [14], and reported a novel technique for drug administration [15] and described the absorption of a variety of test compounds. The studies conducted in this model have been reviewed recently, along with a pharmacokinetic model developed to describe the disposition of the drugs administered via this route [119],... 

Risk Assessment. This model successfully described the disposition of chloroform in rats, mice and humans following various exposure scenarios and developed dose surrogates more closely related to toxicity response. With regard to target tissue dosimetry, the Corley model predicts the relative order of susceptibility to chloroform toxicity consequent to binding to macromolecules (MMB) to be mouse > rat > human. Linking the pharmacokinetic parameters of this model to the pharmacodynamic cancer model of Reitz et al. (1990) provides a biologically based risk assessment model for chloroform. 

Interroute Extrapolation. The Corley model used three routes of administration, intraperitoneal, oral and inhalation, in rats and mice to describe the disposition of chloroform. This data was validated for humans by comparing the model output using the animal data with actual human data from human oral chloroform pharmacokinetic studies. Using the human pharmacokinetic constants from the in vitro studies conducted by Corley, the model made adequate predictions of the amount of chloroform metabolized and exhaled in both males and females. 

Two other methods have been described that require modelling of the disposition pharmacokinetics but not of the absorption phase. For drugs with disposition pharmacokinetics that can be approximated by a one-compartment model, i.e., the declining part of the plasma concentration-time curve can be approximated by a one log-linear phase, the following equation can be applied to determine the fractional amount absorbed (A) at different times t after administration (Wagner and Nelson 1963) ... 

Physiological toxicokinetic (or pharmacokinetic) models represent descriptions of biological systems and can be used to describe the behaviour of chemicals in the intact animal. Such models have been used to predict the disposition of butadiene and metabolites in rats, mice, and humans. For the case of rats and mice, these predictions can be compared with experimental data. In some cases (see below), the models successfully describe (and accurately predict) the disposition of butadiene and metabolites. Human physiological toxicokinetic model predictions normally cannot be verified due to lack of experimental data. 

Physiologically based pharmacokinetic (PBPK) models use mathematical descriptions of the uptake and disposition of chemical substances to quantitatively describe the relationships among critical biological... 

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