Phospholipids, absorption

The major lipids in the diet are triacylglycerols and, to a lesser extent, phospholipids. These are hydrophobic molecules and must be hydrolyzed and emulsified to very small droplets (micelles) before they can be absorbed. The fat-soluble vitamins— A, D, E, and K— and a variety of other lipids (including cholesterol) are absorbed dissolved in the lipid micelles. Absorption of the fat-soluble vitamins is impaired on a very low fat diet. 

Baskaran, V, Sugawara, T., and Nagao, A., Phospholipids affect the intestinal absorption of carotenoids in mice. Lipids, 38, 705, 2003. 

Highly insoluble molecules are in part transported in the GIT by partitioning into the mixed micelles injected into the lumen from the biliary duct in the duodenum (Fig. 2.3). Mixed micelles consist of a 4 1 mixture of bile salts and phospholipids (Fig. 7.13). In contrast, at the point of absorption in the BBB, highly insoluble molecules are transported by serum proteins. This distinction is expected to be important in in vitro assay modeling. The use of simulated intestinal fluids is appealing. 

This book is written for the practicing pharmaceutical scientist involved in absorption-distribution-metabolism-excretion (ADME) measurements who needs to communicate with medicinal chemists persuasively, so that newly synthesized molecules will be more drug-like. ADME is all about a day in the life of a drug molecule (absorption, distribution, metabolism, and excretion). Specifically, this book attempts to describe the state of the art in measurement of ionization constants (p Ka), oil-water partition coefficients (log PI log D), solubility, and permeability (artificial phospholipid membrane barriers). Permeability is covered in considerable detail, based on a newly developed methodology known as parallel artificial membrane permeability assay (PAMPA). 

DA Whitmore, LG Brookes, KP Wheeler. (1979). Relative effects of different surfactants on intestinal absorption and the release of proteins and phospholipids from the tissue. J Pharm Pharmacol 31 277-283. 

The monomolecular solution of the phospholipid enantiomer, (R)-3.15, in MeOH is optically inactive. Surprisingly, when (R)-3.15 was dispersed in water, distinct CD bands were seen, Figure 3.10. The calculation of the absorption band resulted in a tetramer with H-type and /-type... 

Copper deficiency in humans and other mammals is characterized by slow growth, hair loss, anemia, weight loss, emaciation, edema, altered ratios of dietary copper to molybdenum and other metals, impaired immune response, decreased cytochrome oxidase activity, central nervous system histopathology, decreased phospholipid synthesis, fetal absorption, and eventually death (NAS 1977 Gallagher 1979 Kirchgessner et al. 1979 USEPA 1980 ATSDR 1990 Percival 1995). 

Wohnsland and Faller ([175] performed measurements using a thin (9-10 //in) supported, phospholipid-free hexadecane layer. To validate their model, they used 32 well-characterized chemically diverse compounds. The permeability values obtained with their model could be correlated with known human absorption values if the maximum permeability obtained at different pH was taken into account. However, several disadvantages are related to this method. For hydrophilic drugs, hexadecane by itself has an increased barrier function in comparison with membranes. In addition, the hexadecane layers are not very stable, which makes this assay difficult to apply as a routine screening method. The advantage of this PAMPA setup is that it appears to be a satisfactory substitute for obtaining alkane-water partition coefficients, which are usually very difficult to measure directly, due to the poor solubility of drug molecules in alkanes. 

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