Absorption kinetics approach

For example, for alkyl (8-16) glycoside (Plantacare 818 UP) non-ionic surfactant solution of molecular weight 390 g/mol, an increase in surfactant concentration up to 300 ppm (CMC concentration) leads to a significant decrease in surface tension. In the range 300 < C < 1,200 ppm the surface tension was almost independent of concentration. In all cases an increase in liquid temperature leads to a decrease in surface tension. This surface tension relaxation is a diffusion rate-dependent process, which typically depends on the type of surfactant, its diffusion/absorption kinetics, micellar dynamics, and bulk concentration levels. As the CMC is approached the absorption becomes independent of the bulk concentration, and the surfactant... 

The previous section presented a simplified (and perhaps somewhat idealized) picture of the mechanism-based modeling approach. To provide a more concrete example let us consider the problem of modeling the absorption kinetics of subcutaneously injected soluble insulin [11]. 

These linear kinetic models and diffusion models of skin absorption kinetics have a number of features in common they are subject to similar constraints and have a similar theoretical basis. The kinetic models, however, are more versatile and are potentially powerful predictive tools used to simulate various aspects of percutaneous absorption. Techniques for simulating multiple-dose behavior evaporation, cutaneous metabolism, microbial degradation, and other surface-loss processes dermal risk assessment transdermal drug delivery and vehicle effects have all been described. Recently, more sophisticated approaches involving physiologically relevant perfusion-limited models for simulating skin absorption pharmacokinetics have been described. These advanced models provide the conceptual framework from which experiments may be designed to simultaneously assess the role of the cutaneous vasculature and cutaneous metabolism in percutaneous absorption. 

Pharmacokinetic Tools to Characterize Absorption Kinetics. The sustained character of lung absorption is important for the degree of pulmonary selectivity. It is therefore important to evaluate lung absorption with pharmacokinetic tools. Several tools have been used to provide this information, including the time to reach the maximum plasma concentration (tmax), the mean absorption time (MAT), flip-flop, and deconvolution. These approaches are described next. 

Guy RH, Hadgraft J, Maibach HI. 1985. Percutaneous absorption in man A kinetic approach. Toxicol Appl Pharmacol 78 123-129. 

Despite the errors that can arise in both the Forster cycle and the steady-state fluorescence the pAT obtained by both methods usually agree to within 1 or 2 pK units (see tables in Ref. 28). For triplet states appUcation of either method is often difficult or even impossible. Instead it is necessary to use a kinetic approach. The amounts of conjugate acid and base in the triplet state are followed by time-resolved excited-state absorption spectroscopy. ... 

PDMS membranes have been widely used as a skin imitation membrane for dermal absorption studies (Moss et al., 2002). A membrane-coated fiber technique has bear developed in our center for quantitative analysis of the absorption kinetics and rapid determination of the partition coefficients of chemicals between the PDMS membrane and chemical mixtures (Xia et al., 2003). In the following sections, the system coefficient approach is demonstrated by measuring the partition coefficients of chemicals in the P/W systems. 

The physicochemical approach to the prediction of transdermal absorption kinetics described In this paper offers a promising stategy for the estimation of cutaneous exposure risk. The model Is conceptually straightforward yet sensitive to the biology of skin and to the chemical and physical properties of the penetrant. Human, In vivo, penetration data for a diverse array of absorbing molecules have been... 

Fisher RB, Gardner ML. A kinetic approach to the study of absorption of solutes by isolated perfused small intestine. J Physiol 1974 241 211-234. 

As projects approach decision points regarding oral absorption solubihty assays must change towards the traditional thermodynamic equilibrium solubihty assay. Stated again for emphasis - the early discovery kinetic solubihty assay is not a replacement for a traditional thermodynamic equilibrium solubihty assay. Accurate oral absorption requires testing of crystalline materials and corresponding accurate solubihty testing of crystalline materials. 

The original proposal of the approach, supported by a Monte Carlo simulation study [36], has been further validated with both pre-clinical [38, 39] and clinical studies [40]. It has been shown to be robust and accurate, and is not highly dependent on the models used to fit the data. The method can give poor estimates of absorption or bioavailability in two sets of circumstances (i) when the compound shows nonlinear pharmacokinetics, which may happen when the plasma protein binding is nonlinear, or when the compound has cardiovascular activity that changes blood flow in a concentration-dependent manner or (ii) when the rate of absorption is slow, and hence flip-flop kinetics are observed, i.e., when the apparent terminal half-life is governed by the rate of drug input. 

It therefore became more convenient to monitor the reaction progress with UV/Visible spectrophotometry, because all the pyridine N-oxides have strong absorption bands near 330 nm, with e 103Lmol 1cm 1. Two approaches for the analysis of the kinetic data were used. In the first but much less precise method, the initial reaction rates were calculated from the objective method of fitting the experimental values of [PyOL to this function (30) ... 

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