Drugs transfer through membranes

Beckett AH, Triggs EJ (1967) Buccal absorption of basic drugs and its application as an in vivo model of passive drug transfer through lipid membranes. J Pharm Pharmacol 19 31S-41S... 

The membrane plays a passive role in drug absorption during passive diffusion most drugs pass through membrane by this mechanism. The rate of drug transfer is determined by the physicochemical properties of the drug and the drug... 

The placental membranes are also lipoidal in nature and lipophilic drugs (also nonlipid soluble drugs to some extent) can easily cross the placental barrier. It is a contact between the foetal blood and the maternal blood. Drugs are transferred through this barrier by simple diffusion method, once across this, drug molecules circulate in the foetal blood before diffusing back. 

Although the drug is mainly transferred through the cell membrane in its free base form, administration of the drug in alkaline solution docs nut enhance its activity. This is because the structure of the drug is controlled by the pH of the extracellular fluid and not the pH uf the dosage form. Once inside the neuron, equilibrium is reestablished. Both the free base and its protonated form are known to be active, but it is not known whether they bind to the same receptor site. However, it does appear that the protonated ba.se plays the major part in anesthetic activity. "... 

The principal biological interest of P values is as models for the penetration of drugs through membranes, but to obtain this type of information presents great experimental difficulties. At least we know that the partition coefficients of a series of alcohols between red cell ghosts and water shows a free energy of about —690 cal/mol for the transfer of each methylene group, approximately the same result as between octanol and water (Seeman, Roth and Schneider, 1971). 

Numerous studies on the influence of surfactants on drug absorption have shown that they can increase, decrease or exert no effect on the transfer of drugs through membranes [14]. As discussed above, the presence of surfactant affects the dissolution rate of the drug, although the effect is less than predicted by the... 

A CRO may also allow for the in-house introduction of specialized lipophilic scales by transferring routine measurements. While the octanol-water scale is widely applied, it may be advantageous to utilize alternative scales for specific QSAR models. Solvent systems such as alkane or chloroform and biomimetic stationary phases on HPLC columns have both been advocated. Seydel [65] recently reviewed the suitabihty of various systems to describe partitioning into membranes. Through several examples, he concludes that drug-membrane interaction as it relates to transport, distribution and efficacy cannot be well characterized by partition coefficients in bulk solvents alone, including octanol. However, octanol-water partition coefficients will persist in valuable databases and decades of QSAR studies. 

A thorough discussion of the mechanisms of absorption is provided in Chapter 4. Water-soluble vitamins (B2, B12, and C) and other nutrients (e.g., monosaccharides, amino acids) are absorbed by specialized mechanisms. With the exception of a number of antimetabolites used in cancer chemotherapy, L-dopa, and certain antibiotics (e.g., aminopenicillins, aminoceph-alosporins), virtually all drugs are absorbed in humans by a passive diffusion mechanism. Passive diffusion indicates that the transfer of a compound from an aqueous phase through a membrane may be described by physicochemical laws and by the properties of the membrane. The membrane itself is passive in that it does not partake in the transfer process but acts as a simple barrier to diffusion. The driving force for diffusion across the membrane is the concentration gradient (more correctly, the activity gradient) of the compound across that membrane. This mechanism of... 

The processes of pharmacokinetics all involve the transfer of a drug across membranes, beginning with the cell membrane, and sometimes involving single or multiple layers of cells. Drugs can cross these membranes through passive or active transport. 

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