Estimation in-vivo

Permeability is a kinetic property expressed by the permeability coefficient (centimeters per second), a number indicating the rate at which molecules pass from aqueous solution across a membrane to another solution on the other side. Permeability is a molecular property used to screen for more complex absorption processes (i.e. in vitro permeabihty is measured to estimate in vivo absorption). 

In practice, estimation of Laq requires information on the rate of solute removal at the membrane since aqueous resistance is calculated from experimental data defining the solute concentration profile across this barrier [7], Mean /.aq values calculated from the product of aqueous diffusivity (at body temperature) and aqueous resistance obtained from human and animal intestinal perfusion experiments in situ are in the range of 100-900 pm, compared to lumenal radii of 0.2 cm (rat) and 1 cm (human). These estimates will necessarily be a function of perfusion flow rate and choice of solute. The lower Laq estimated in vivo is rationalized by better mixing within the lumen in the vicinity of the mucosal membrane [6],... 

Loss of radioactive material from the skin surface has been used to estimate in vivo percutaneous absorption. The difference in applied dose and residue on the skin is assumed to be absorbed. The characteristics of the radioisotope, penetrant, and vehicle may limit the usefulness of this procedure. Volatile materials may leave the surface without penetrating, and it is difficult to recover all material from the skin surface. In addition, skin may retain a reservoir of the penetrant that has not entered the circulation. 

Though it was realized very early that microdialysis can serve as an excellent tool for estimating in vivo enzymatic activities (Sharp et al., 1986), this application remained relatively unexplored until recently (Westerink et al., 1990). Microdialysis offers several advantages over existing in vitro techniques because it affords the opportunity for continuous sampling from organs other than blood and because of its high spatial resolution. 

Robert F, Lambassenas L, Ortemann C, Pujol JF, Renaud B (1993) Microdialysis monitoring of 3,4-dihydroxyphenylalanine accumulation after decarboxylase inhibition—A means of estimate in vivo changes in tyrosine hydroxylase activity of the rat locus ceruleus. J Neurochem 60 721-729. 

Various methods have been developed to estimate in vivo BBB drug transport also. The applicability of these methods depends on their sensitivity and selectivity to measure dmg concentrations in the brain, the estimation of local concentrations in the brain (spatial resolution), and the measurement of single-time concentrations versus concentration-time profiles (time resolution). Because an extended discussion is beyond the scope of this review, the reader is referred to the literature (32). 

Scaling Factors and Liver Blood Flow for Estimating In Vivo Hepatic Clearance from In Vitro Intrinsic CL... 

Application of emerging technologies allows the optimization of potency and efficacy while monitoring potential adverse interactions of new chemicals with biological systems. In addition, it is possible to develop structure activity versus structure toxicity relationships, develop in vitro margins of safety, estimate a therapeutic index, and use in vitro data to estimate in vivo toxicity. 

A general issue with P450 2C9, because of its relatively high abundance (Figures 10.1 and 10.4), is its role in reducing bioavailability. However, estimating in vivo pharmacokinetic properties from in vitro data is still not trivial. Houston has reviewed the issue with P450 2C9 recentl). ... 

In this context, the quantitative structure-activity relationship (QSAR) technique has become the standard European Commission-approved computational/m silica method for estimating in vivo/in vitro experiments regarding chemical toxicity for... 

De Jongh J, Verhaar HJM, Hermes JLM. 1997. A quantitative property relationship (QSPR) approach to estimate in vivo tissue blood partition coefficients of organic chemicals in rats and humans. Arch Toxicol 72 17-25. 

NIH. Guidance document on using in vitro data to estimate in vivo starting doses for acute toxicity. NIH Publication No 01-4500. 2001. http //ntp.niehs.nih.gov/iccvam/docs/acutetox docs/guidance0801/iv guide.pdf (accessed on October 13, 2015). 

Whether or not the in vitro test results of the myocardial properties are applicable for the in vivo cardiac analyses remains as a heated debate topic. As has already been discussed earlier, the finite element models enable te myocardial passive and active characteristics to be estimated in vivo. It is an inverse problem of knowing the loading and the consequent deformation and of continuously guessing the material properties until the simulated and measured deformations are approximately matched. 

Chi a fluorescence is a property exhibited by all photosynthetic organisms due to the essential role of chlorophyll in the structure and function of the photosynthetic apparatus. Typically less than 3% of the absorbed light is ever re-emitted as chlorophyll fluorescence and, at room temperature, the latter primarily emanates from PSII (Krause and Jahns, 2003). Quantification of chlorophyll a fluorescence induction has proven to be an extremely useful tool to assess the structure and ftmction of PSII and the overall process of photosynthesis (Krause and Weis, 1991 Krause and Jahns, 2003). Since reduced Qb is in equilibrium with the reduced PQ pool, the relative reduction state of the PQ pool, also called excitation pressure, can be estimated in vivo as the relative reduction state of Qa, that is [Qa ] / ([Qa] + [Qa ]), which can be conveniently measured in vivo as 1-qP using pulse amplitude modulated... 

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