Absorption passive

ACS Symposium Series American Chemical Society Washington, DC, 1980, 

Acetyl coenzyme A synthetase 6.2.1.1 Bovine heart mitochondria 

Arglnase 3.5.3.1. Bovine liver Canavalia enslformls Jack bean Yeast 

Ascorbic acid oxidase 1.10.3.3 Broad bean leaf 

Urease 3.5.1.5 Jack bean Lemna paucicostata Rumen bacterial Soybean 

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AM columns are another means of measuring lipophilic characteristics of drug candidates and other chemicals [99-103]. 1AM columns may better mimic membrane interactions than the isotropic octanol-water or other solvent-solvent partitioning system. These chromatographic indices appear to be a significant predictor of passive absorption through the rat intestine [128]. 

Kansy, M., Senner, F., Gubemator, K. Physicochemical high throughput screening parallel artificial membrane permeation assay in the description of passive absorption processes. /. Med. Chem. 1998, 43, 1007-1010. 

Another important type of physical chemical interaction that may alter absorption is that of drug binding or adsorption onto the surface of another material. As with complexation and micellarization, adsorption will reduce the effective concentration gradient between gut fluids and the bloodstream, which is the driving force for passive absorption. While adsorption frequently reduces the rate of absorption, the interaction is often readily reversible and will not affect the extent of absorption. A major exception is adsorption onto charcoal, which in many cases appears to be irreversible, at least during the time of residence within the GIT. As a result, charcoal often reduces the extent of drug absorption. Indeed, this fact... 

In this book we will focus on physicochemical profiling in support of improved prediction methods for absorption, the A in ADME. Metabolism and other components of ADME will be beyond the scope of this book. Furthermore, we will focus on properties related to passive absorption, and not directly consider active transport mechanisms. The most important physicochemical parameters associated with passive absorption are acid-base character (which determines the charge state of a molecule in a solution of a particular pH), lipophilicity (which determines distribution of a molecule between the aqueous and the lipid environments), solubility (which limits the concentration that a dosage form of a molecule can present to the solution and the rate at which the molecule dissolves from... 

Zhu, C. Chen, T.-M. Hwang, K., A comparative study of parallel artificial membrane permeability assay for passive absorption screening, in CPS A2000 The Symposium on Chemical and Pharmaceutical Structure Analysis. Milestone Development Services. Princeton, NJ, Sept. 26-28, 2000. 

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. 

Water and electrolytes. Each day in an average adult, about 5.51 of food and fluids move from the stomach to the small intestine as chyme. An additional 3.5 1 of pancreatic and intestinal secretions produce a total of 9 1 of material in the lumen. Most of this (>7.5 1) is absorbed from the small intestine. The absorption of nutrient molecules, which takes place primarily in the duodenum and jejunum, creates an osmotic gradient for the passive absorption of water. Sodium may be absorbed passively or actively. Passive absorption occurs when the electrochemical gradient favors the movement of Na+ between the absorptive cells through "leaky" tight junctions. Sodium is actively absorbed by way of transporters in the absorptive cell membrane. One type of transporter carries a Na+ ion and a Cl ion into the cell. Another carries a Na+ ion, a K+ ion, and two Cl ions into the cell. 

Porter, J. L., Fordtran, J. S., Mechanism by which glucose stimulates the passive absorption of small solutes by the human jejunum in vivo, Gastroenterology 1994, 307, 389-395. 

Figure 2.3 Schematic diagram of the method approach in optimising the drug design for passive absorption by determining the additional hpophihcity required to raise the absorption rate constant of the lead candidate in dilute solution to >90% of the maximum (Adapted from Ho et al. [5]).

Figure 2.11 A comparison between human and rat effective intestinal permeability coefficients (Peff). The equation describes the correlation for passive diffusion. The inset shows the Peff values in the lower range ( = passive absorption A = carrier-mediated absorption) [46, 47],...

The concentration gradient across the intestinal mucosa, being the driving force for passive absorption, is affected by the thermodynamic solubility and dissolution rate of the drug in the intestinal fluids as described earlier. 

Fine, K.D., Santa Ana, C.A., Porter, J.L., and Fordtran, J.S., Effect of D-glucose on intestinal permeability and its passive absorption in human small intestine in vivo, Gastroenterology, 105, 1117, 1993. 

Abbreviations Sol, aqueous solubility F, bioavailability PPB, plasma protein binding Met, metabolism Tox, toxicity PA, passive absorption AP, apparent permeability. 

Kansy M., Sermer, F. and Gubernator, K. (1998) Physicochemical High Throughput Screening Parallel Artificial Membrane Permeation Assay in the Description of Passive Absorption Processes. Journal of Medicinal Chemistry, 41, 1007-1010. 

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