Transport of drugs

Shitara Y, Sato H, Sugiyama Y (2005) Evaluation of drug-drug interactions in the hepatobiliary and renal transport of drugs. Annu Rev Pharmacol Toxicol 45 689-723... 

The evaluation of the apparent ionization constants (i) can indicate in partition experiments the extent to which a charged form of the drug partitions into the octanol or liposome bilayer domains, (ii) can indicate in solubility measurements, the presence of aggregates in saturated solutions and whether the aggregates are ionized or neutral and the extent to which salts of dmgs form, and (iii) can indicate in permeability measurements, whether the aqueous boundary layer adjacent to the membrane barrier, Umits the transport of drugs across artificial phospholipid membranes [parallel artificial membrane permeation assay (PAMPA)] or across monolayers of cultured cells [Caco-2, Madin-Darby canine kidney (MDCK), etc.]. 

Fig. 9 Schematic representation depicting the movement of molecules from the absorbing (mucosal or apical) surface of the GIT to the basolateral membrane and from there to blood. (A) transcellular movement through the epithelial cell. (B) Paracellular transport via movement between epithelial cells. (Q Specialized carrier-mediated transport into the epithelial cell. (D) Carrier-mediated efflux transport of drug out of the epithelial cell. (Copyright 2000 Saguaro Technical Press, Inc., used with permission.)...

Up to now we have focused on measurement of permeability and membrane retention at pH 7.4. Since the GIT covers a range of pH values, with pH 5-8 characterizing the small intestine, it is necessary to address the pH dependence of the transport of drug molecules. Even nonionizable molecules may be affected by pH dependence, since several biological membrane components themselves are ionizable (pKa values listed in Fig. 7.4). For example, with PS, PA, and DA (free fatty acid) undergoing changes in charge state in the pH 5-8 interval. In this section, we examine the consequences of pH dependence. 

Artursson, R, Epithelial transport of drugs in cell culture. I A model for studying the passive diffusion of drugs over intestinal absorptive (Caco-2) cells, J. Pharm. Sci. 79, 476-482 (1990). 

Membrane transport of drugs by both linear and nonlinear mechanisms is represented by addition of Eqs. (19) and (20). 

S. J., Goldenberg, S., Wiliams, C., Pasatan, I., Gottesman, M. M., Handler, J., Transepithelial transport of drugs by the multidrug transporter in cultured Madin-Darby canine kidney cell epifhelia, J. Biol. Chem. 1989, 264, 14880-14884. 

Tsuji, A., Tamai, I., Carrier-mediated intestinal transport of drugs, Pharm. Res. 1996, 33, 963-977. 

Fig. 7.1. The intestinal permeability of drugs in vivo is the total transport parameter that may be affected by several parallel transport mechanisms in both absorptive and secretory directions. Some of the most important transport proteins that may be involved in the intestinal transport of drugs and their metabolites across intestinal epithelial membrane barriers in humans are displayed.

A direct in vivo assessment of the quantitative importance of gut wall metabolism and transport of drugs and metabolites in humans is difficult and consequently has been attempted only rarely [3, 6, 11, 12, 15, 16, 23, 25-32, 34, 35, 81]. The most direct in vivo approach to investigating these processes in drugs with variable and incomplete bioavailability was intestinal perfusion by single-pass per-... 

Investigations of regional differences in permeability and metabolism have been carried out using a variety of animal models [22, 29, 75, 102, 109, 112, 137]. Animal tissues (mainly from rats) are widely used in the Ussing chamber to investigate intestinal transport of drugs, and regional aspects [29, 75, 138], whereas few studies have been conducted with human tissues due to their limited availability. 

Ungell, A. L., Nyiander, S., Bergstrand, S., Sjoberg, A., Lennernas, H., Membrane transport of drugs in different regions of the intestinal tract of the rat, J. Pharm. 

Suzuki, H., Sugiyama, Y., Transport of drugs across the hepatic sinusoidal membrane sinusoidal drug influx and efflux in the liver, Semin. Liver Dis. 2000, 20, 251-263. 

Bohan, A., Boyer, J. L., Mechanism of hepatic transport of drugs implications for cholestatic drug reactions, Semin. Liv. Dis. 2002, 22, 123-136. 

Evans, A. M., Influence of dietary components on the gastrointestinal metabolism and transport of drugs, Therap. Drug Monitor. 2000, 22, 131— 136. 

Lipophilicity is an important property of molecules in relation to their biological activities. It is one of the key physiochemical parameters that determine the distribution and transport of drugs into the body and target organs. Measurements of lipophilicity, expressed as the logarithm of the... 

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