Gastrointestinal absorption research

Octanol/water partition (log P) and distribution (log D) coefficients are widely used to make estimates for membrane penetration and permeability, including gastrointestinal absorption [40, 41], blood-brain barrier (BBB) crossing [42, 43], and correlations to pharmacokinetic properties [1], In 1995 and 2000, specialized but very well attended meetings were held to discuss the role of log P in drug research [44, 45]. 

An age-related difference in the extent of gastrointestinal absorption of chromium(III) was reported in one study (Sullivan et al. 1984) it is not known if a similar relationship would exist for chromium(VI). No other information is available which evaluated potential differences between adults and children. Toxicokinetic studies examining how aging can influence the absorption, distribution, and excretion of chromium, particularly chromium(VI) would be useful in assessing children s susceptibility to chromium toxicity. There are no data to determine whether there are age-specific biomarkers of exposure or effects or any interactions with other chemicals that would be specific for children. There is very little available information on methods for reducing chromium toxic effects or body burdens it is likely that research in adults would also be applicable to children. 

Harrison JD, Slather JW. 1981. The gastrointestinal absorption of proactinium, uranium and neptunium in the hamster. Radiation Research 88 47-55. 

Larsen RP, Bhattachyaryya MH, Oldham RD, et al. 1984. Gastrointestinal absorption and retention of plutonium and uranium in the baboon. Division of Biological and Medical Research. Institute of Environmental Medicine, New York University Medical Center, Tuxedo, New York, 51-60. 

Suttle, A.B., Pollack, G.M. and Brouwer, K.L. (1992) Use of a pharmacokinetic model incorporating discontinuous gastrointestinal absorption to examine the occurrence of double peaks in oral concentration-time profiles. Pharmaceutical Research, 9 (3), 350-356. 

Anna-Lena Ungell, PhD, is associate director of DMPK and bioanalytical chemistry at AstraZeneca R D Molndal. She supports preclinical and pharmaceutical projects relating to absorption as well as the gastrointestinal absorption of drugs. Her experience includes absorption models, mechanisms of drug absorption from the intestinal tract, substance evaluation and basic formulation development. Dr. Ungell has four patents and has written numerous research articles and reviews. 

Innovative research is also ongoing to characterize natural product-derived substances that prevent the gastrointestinal absorption of alcohol, and limit CNS receptor super-sensitivity responses to chronic methamphetamine abuse. Development of pharmacologic treatments that could effectively and safely achieve either goal would be of enormou spotential consequence in the management of two of the most intractable and costly substance abuse problems in the U.S, namely alcoholism and methamphetamine abuse. 

Weeks M, Ballou J, Thompson R. 1956. Effect of chemical and physical state on gastrointestinal absorption of plutonium. Biology Research Annual Report 1955 to U.S. Atomic Energy Commission, Washington, DC, by Hanford Atomic Products Operatiorl, Richard, WA. Report HW41500. 

Investigations, particularly in the field of occupational medicine [5-7], indicate a direct absorption of inhaled aluminum in the lungs. The amount of the absorbed aluminum seems to be dependent on the respective size of particles. A few research groups, however, discuss a secondary gastrointestinal absorption of inhaled aluminum [8]. Functionally, it is assumed that aluminum particles are transported via the absorption epithelium of the respiratory tracts in the direction of the pharynx and then swallowed. The amount of inhaled aluminum dust from the environment can be neglected according to the present state of knowledge. 

Stirred tank models have been widely used in pharmaceutical research. They form the basis of the compartmental models of traditional and physiological pharmacokinetics and have also been used to describe drug bioconversion in the liver [1,2], drug absorption from the gastrointestinal tract [3], and the production of recombinant proteins in continuous flow fermenters [4], In this book, a more detailed development of stirred tank models can be found in Chapter 3, in which pharmacokinetic models are discussed by Dr. James Gallo. The conceptual and mathematical simplicity of stirred tank models ensures their continued use in pharmacokinetics and in other systems of pharmaceutical interest in which spatially uniform concentrations exist or can be assumed. 

Wilhnarm, S., Schmitt, W., Keldenich, J. and Dressman, J.B. (2003) A physiologic model for simulating gastrointestinal flow and drug absorption in rats. Pharmaceutical Research, 20, 1766-1771. 

Macheras, P. and Argyrakis, P., Gastrointestinal drug absorption Is it time to consider heterogeneity as well as homogeneity Pharmaceutical Research, Vol. 14, 1997, pp. 842-847. 

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