Absorption simulation

GastroPlus [137] and IDEA [138] are absorption-simulation models based on in vitro input data like solubility, Caco-2 permeability and others. They are based on advanced compartmental absorption and transit (ACAT) models in which physicochemical concepts are incorporated. Both approaches were recently compared and are shown to be suitable to predict the rate and extent of human absorption [139]. 

We demonstrated the utility of GI absorption simulation based on the ACAT in predicting the impact of physiological and biochemical processes on oral dmg bioavailability [44, 45]. 

Wade et al. (1993) simulated concentration data for 100 subjects under a one-compartment steady-state model using either first-or zero-order absorption. Simulated data were then fit using FO-approximation with a first-order absorption model having ka fixed to 0.25-, 0.5-, 1-, 2-, 3-, and 4 times the true ka value. Whatever value ka was fixed equal to, clearance was consistently biased, but was relatively robust with underpredictions of the true value by less than 5% on average. In contrast, volume of distribution was very sensitive to absorption misspecification, but only when there were samples collected in the absorption phase. When there were no concentration data in the absorption phase, significant parameter bias was not observed for any parameter. The variance components were far more sensitive to model misspecification than the parameter estimates with some... 

Joly Y, Cabaret D, Renevier H, Natoli CR (1999) Electron population analysis by full-potential X-ray absorption simulations. Phys Rev Lett 82 2398-2401... 

Model simulations (see chapter 4.4) substantiate that the lipophilicity dependence of the rate constants of drug transport should follow bilinear relationships [41,156, 175,345,440,442]. Indeed, bilinear equations have been derived for the rate constants of drug transport in n-octanol/water (eqs. 95 — 98, chapter 4.4) [444 —447] and for the rate constants of the transfer of various barbiturates (38) in a Sartorius absorption simulator from an aqueous phase (pH = 3) through an organic membrane to another aqueous phase (pH = 7.5), modeling the gastric absorption of these compounds (Figure 41) (eq. 162 recalculated optimum log P value) [442]. 

Figure 41 Diffusion rate constants log k of barbiturates (38) in the Sartorius absorption simulator (eq. 162) (reproduced from Figure 11 of ref. [442] with permission from Editio Cantor Verlag GmbH, Aulendorf, Germany).

In order to investigate the effect of the competing agent on the in vitro membrane permeability of CN, the apparent penetration rate constant was determined using a Sartorious Absorption Simulator (lOd). The experiment was done also in comparison with L-isoleucine and L-leucine. 

Stolzberg, R. J. Screening and Sequential Experimentation Simulations and Elame Atomic Absorption Spectrometry Experiments, /. Chem. Educ. 1997, 74, 216-220. 

Durability. Grass-like surfaces intended for heavy-duty athletic use should have a service life of at least eight years, a common warranty period provided by suppHers. Lifetime is more or less proportional to the ultraviolet (uv) exposure (sunlight) and to the amount of face ribbon available for wear, but pile density and height also have an effect. Color is a factor generally uv absorption is highest with red fabrics and least with blue. In addition, different materials respond differendy to abrasive wear. These effects caimot be measured except in simulated field use and controlled laboratory experiments, which do not necessarily redect field conditions. 

A study of industrial apphcatious by Taylor, Kooijmau, and Woodman [IChemE. Symp. Ser. Distillation and Absorption 1992, A415-A427 (1992)] concluded that rate-based models are particularly desirable when simulating or designing (1) packed columns, (2) systems with strongly uonide liquid solutions, (3) systems with trace compo-... 

Enhancing the Profitability of Lean Oil Absorption Through Simulation, GasTIPS , Fail 1996, Volume 2, Number 3, p.38... 

On the basis of the optimized ground-slate geometries, we simulate the absorption speetra by combining the scmicmpirical Hartree-Fock Intermediate Neglect of Differential Overlap (INDO) Hamiltonian to a Single Configuration Interaction... 

In-vitro models can provide preliminary insights into some pharmacodynamic aspects. For example, cultured Caco 2 cell lines (derived from a human colorectal carcinoma) may be used to simulate intestinal absorption behaviour, while cultured hepatic cell lines are available for metabolic studies. However, a comprehensive understanding of the pharmacokinetic effects vfill require the use of in-vivo animal studies, where the drug levels in various tissues can be measured after different dosages and time intervals. Radioactively labelled drugs (carbon-14) may be used to facilitate detection. Animal model studies of human biopharmaceutical products may be compromised by immune responses that would not be expected when actually treating human subjects. 

Example 11.7 hints at the complications that are possible in reactive gas absorption. Gas absorption is an important unit operation that has been the subject of extensive research and development. Large, proprietary computer codes are available for purchase, and process simulation tools such as Aspen can do the job. However, as shown in Example 11.8, simple but useful approximations are sometimes possible. 

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