Membrane drug distribution

Barton, P. Davis, A. M. McCarthy, D. J. Webbom, P. J. H., Drug-phospholipid interactions. 2. Predicting the sites of drug distribution using n-octanol/water and membrane/water distribution coefficients. J. Pharm. Set 86, 1034—1039 (1997). 

Some idea of the rate of absorption can be obtained from examination of the plasma concentration-time profile. It should be remembered, however, that the time to maximum plasma concentration Y ) is not when absorption is complete but when the rates of drug absorption and elimination are equal. Thus two drugs with the same absorption rate will differ in /max if elimination rates differ. Assessment of the rate of absorption can also be confounded by complex or slow drug distribution. For example, the calcium-channel blocker amlodipine has a much later /max than other similar drugs. This is not due to slow absorption but to partitioning in the liver membrane with slow redistribution. A quantitative assessment of the rate of absorption can be obtained by deconvolution of plasma profiles following IV and oral administration. 

Mechanisms involved in the passage of drugs across membranes. (Adapted with permission from Smyth DH. Absorption and Distribution of Drugs. Baltimore Williams Wilkins, 1964 and Forth W and Rummel W (eds.). Pharmacology of Intestinal Absorption Gastrointestinal Absorption of Drugs. Vols. 1 and 2. Oxford, UK Pergammon, 1975). 

The circulatory system of fish is also unique structurally and functionally. Structurally, the membranous nature of the vasculature makes for a friable high-capacitance system under low pressure. Low blood flows result in somewhat longer distributional phases for many drugs. Processes such as heart rate and stroke volume that influence drug distribution are themselves influenced by external factors such as temperature and stress. In addition, total plasma protein content differs in fish as compared to mammals. Total plasma protein in the trout and flounder is approximately one-half that of mammals such as dogs and cats. For many compounds protein binding is considerably lower in fish than their mammalian counterparts (19, 20). 

The increase in vaginal fluids due to estrogens and sexual stimulations improve the absorption of poorly water-soluble drugs on the contrary, a greater presence of mucus on the mucosal membrane slows down the contact between the drug and the absorptive epithelium [3]. Moreover, the vaginal fluids could remove and wash away the formulations from application and action site or cause an erratic drug distribution. Furthermore pH variation,... 

To pass through a membrane (see Appendices 3 and 5) a drug must usually exhibit a reasonable degree of both water and lipid solubility (see section 2.7.1). An appropriate degree of water solubility will often improve drug distribution within the circulatory system as well as drug action. 

Drug-Membrane Interactions Analysis, Drug Distribution, Modeling. Joachim K. Seydel, Michael Wiese 1... 

It is therefore not surprising that in many cases a suitable preparation of liposomes is a better model for describing drug distribution into specific tissues than log Poct. To select the best liposome preparation remains, however, a problem until we know more about the individual composition of biological membranes in different tissues and their possible interaction modes with certain drug structures. 

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