Drug absorption estimation

E. P., McEarland,. W., Schaper, K.-J. Quantitative estimation of drug absorption in humans for passively transported compounds on the basis of their physico-chemical parameters. 

In Drug EioavailabiliPy, Estimation of Solubility, Permeability, Absorption and Bioavailability (Methods and Principles in Medicinal Chemistry), Van der Waterbeemd, H., Lennernas, H., Artursson, P. (eds.), Wiley-VCH, Weinheim, 2003, pp. 358-405. 

Figure 7.15 Kinetics of transport across a filter-immobilized artificial membrane (a) desipramine and (b) dihydromethysticin concentrations in acceptor well. [Reprinted from Avdeef, A., in van de Waterbeemd, H. Lennemas, H. Artursson, R (Eds.). Drug Bioavailability. Estimation of Solubility, Permeability, Absorption and Bioavailability. Wiley-VCH Weinheim, 2003 (in press), with permission from Wiley-VCH Verlag GmbH.]...

Although the pH-partition hypothesis and the absorption potential concept are useful indicators of oral drug absorption, physiologically based quantitative approaches need to be developed to estimate the fraction of dose absorbed in humans. We can reasonably assume that a direct measure of tissue permeability, either in situ or in vitro, will be more likely to yield successful predictions of drug absorption. Amidon et al. [30] developed a simplified film model to correlate the extent of absorption with membrane permeability. Sinko et al. [31] extended this approach by including the effect of solubility and proposed a macroscopic mass balance approach. That approach was then further extended to include facili-... 

Equations (25) and (26) show that the dissolution number will also influence the drug absorption in addition to the absorption and dose numbers. Assuming that the initial amount of drug in solution is insignificant compared to the amount of solid drug, the fraction of dose absorbed can be estimated by... 

The CAT model estimates not only the extent of drug absorption, but also the rate of drug absorption that makes it possible to couple the CAT model to pharmacokinetic models to estimate plasma concentration profiles. The CAT model has been used to estimate the rate of absorption for saturable and region-depen-dent drugs, such as cefatrizine [67], In this case, the model simultaneously considers passive diffusion, saturable absorption, GI degradation, and transit. The mass balance equation, Eq. (51), needs to be rewritten to include all these processes ... 

To predict oral plasma concentration-time profiles, the rate of drug absorption (Eq. (53)) needs to be related to intravenous kinetics. For example, in the case of the one-compartment model with first-order elimination, the rate of plasma concentration change is estimated as... 

The CAT model considers passive absorption, saturable absorption, degradation, and transit in the human small intestine. However, the absorption and degradation kinetics are the only model parameters that need to be determined to estimate the fraction of dose absorbed and to simulate intestinal absorption kinetics. Degradation kinetics may be determined in vitro and absorption parameters can also be determined using human intestinal perfusion techniques [85] therefore, it may be feasible to predict intestinal absorption kinetics based on in vitro degradation and in vivo perfusion data. Nevertheless, considering the complexity of oral drug absorption, such a prediction is only an approximation. 

Drug Bioavailability Estimation of Solubility, Permeability, Absorption and Bioavailability. Edited by Han van de Waterbeemd. Hans Lennernas and Per Artursson Copyright 2003 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN 3-527-30438-X... 

Fagerholm, U., Lennernas, H., Experimental estimation of the effective unstirred water layer thickness in the human jejunum, and its importance in oral drug absorption. Eur. J. Pharm. Sci. 1995, 3, 247-253. 

L. X. Yu, G. L. Amidon. A compart-mental absorption and transit model for estimating oral drug absorption. Int.J. Pharm. 1999, 386, 119-125. 

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