Transport mechanisms drug interactions

Transporter-Mediated Drug Interactions Molecular Mechanisms and Clinical Implications... 

As aforementioned, the underlying mechanisms of many transporter-mediated drug interactions cannot be readily defined because of the interplay between drug... 

Primarily to elucidate transporter localization and function, vesicles enriched in trophoblast apical or basolateral membranes have frequently been utilized. To give a few instances, they have been used to investigate P-gp-mediated transport, mechanisms of transport of cationic compounds, drug interactions with nutrient transport, and differences in amino acid transport in pathological conditions of the placenta [36, 40-42], Briefly, for preparation of microvillus membrane vesicles the cord, amniochorion and decidua are removed from placenta, and the tissue cut on the maternal side. The mince is stirred to loosen... 

From these results it can be concluded that liver slices are a powerful tool for studying the mechanisms and specificity of carrier-mediated uptake of drugs and drug interactions which occur at the transport level. 

Other mechanisms of interaction have also been reported, such as altered activity of other enzymes within the CYP450 family (14—17). Moreover, GFJ may also inhibit the intestinal P-glycoprotein (P-gp)-mediated efflux transport of drugs such as cyclosporine to increase its oral bioavailability (18-21). GFJ and other fruit juices have recently been shown to be potent in vitro inhibitors of a number of organic anion-transporting polypeptides (OATPs) (22,23). 

Because drugs are very reactive, many elicit their effects or side effects, or both, by interacting with coenzymes, enzymes, or nucleic acids, as well as other macromolecules and physiologic processes such as transport mechanisms. To gain an appreciation of the complex interactions between drugs and physiologic parameters, some examples are cited. 

Shitara Y, Itoh T, Sato H, Li AP, Sugiyama Y (2003) Inhibition of transporter-mediated hepatic uptake as a mechanism for drug-drug interaction between cerivas-tatin and cyclosporin A. / Pharmacol Exp Ther 304, 610-616. 

It stands to reason that modulation of intestinal drug-metabolizing enzyme and efflux transporter function could constitute a mechanism of drug-drug interaction. In this chapter, we review the expression and localization of intestinal enzymes and transporters that have been implicated in metabolically based drug-drug interactions and the pharmacokinetic characteristics of those interaction events. 

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