Fraction dose absorbed

PJ Sinko, GD Leesman, GL Amidon. Predicting fraction dose absorbed in humans using a macroscopic mass balance approach. Pharm Res 8(8) 979—988, 1991. 

D Oh, RL Curl, GL Amidon. Estimating the fraction dose absorbed from suspension of poorly soluble compounds in humans A mathematical model. Pharm Res 10 264-270, 1993. 

GL Amidon, PJ Sinko, D Fleisher. Estimating human oral fraction dose absorbed A correlation using rat intestinal membrane permeability for passive and carrier-mediated compounds. Pharm Res 5 651-654, 1988. 

The most useful pharmacokinetic variable for describing the quantitative aspects of all processes influencing the absorption (fa) and first-pass metabolism and excretion (Eg and Eh) in the gut and liver is the absolute bioavailability (F) [40]. This pharmacokinetic parameter is used to illustrate the fraction of the dose that reaches the systemic circulation, and relate it to pharmacological and safety effects for oral pharmaceutical products in various clinical situations. The bioavailability is dependent on three major factors the fraction dose absorbed (fa) and the first-pass extraction of the drug in the gut wall (EG) and/or the liver (EH) (Eq. (1)) [2-4, 15, 35] ... 

Fig. 7.6. a-c. Human in vivo permeabilities (Loc-I-Gut ) (see Fig. 7.4). The major are a cornerstone of the BCS the correlation of advantage of using Peff is that it can be fraction dose absorbed and permeability with measured irrespective of transport mecha-...

Fig. 21.9. A short overview, from in silico to in vivo in humans, of methods available to investigate and predict fraction dose absorbed and bioavailability following oral dosing.

According to the FDA BCS guideline, measurements of the permeability and fraction dose absorbed of a drug can be made by mass balance, absolute bioavailability or intestinal perfusion methods. The intestinal permeability of a drug can be determined by ... 

It is important to recognize that the in vitro permeability obtained in cell mono-layers (such as Caco-2 models) should be considered as a qualitative rather than quantitative value. Especially poor are predictions of fraction dose absorbed for carrier-mediated drugs with low Caco-2 permeability and predictions of high fraction dose absorbed in humans [7, 20, 42, 48, 51]. However, it is possible to establish a reasonably good IVIVC correlation when passive diffusion is the dominating absorption mechanism. 

Fleisher, D., Estimating human oral fraction dose absorbed a correlation... 

Sinko PJ, Leesman GD and Amidon GL (1991) Predicting Fraction Dose Absorbed in Humans Using a Macroscopic Mass Balance Approach. Pharm Res 8 pp 979-988. 

Amidon GL, Sinko PJ and Fleisher D (1988) Estimating Human Oral Fraction Dose Absorbed—A Correlation Using Rat Intestinal-Membrane Permeability for Passive and Carrier-Mediated Compounds. Pharm Res 5 pp 651-654. 

Willman S, Schmitt W, Keldenich J, Lippert J, Dressman JB (2004) A Physiological model for the estimation of the fraction dose absorbed in humans. J. Med. Chem. 47 4022-4031. 

Figure 6.14 Three-dimensional graph of fraction dose absorbed vs. k a and k,i. Dose and cs mjn values [153] correspond to those of digoxin (A) and griseofulvin (B).

Figure 3.2 Graph of estimated fraction dose absorbed (F) vs dissolution number (Dn) and dose number (Do) for a high permeability drug [6], The dose number and the dissolution number ofdigoxin and griseofulvin are marked in the figure.

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