Drug-drag interaction

P-glycoprotein-mediated efflux is a potential source of pecuHarities in drag pharmacokinetics, such as non-Hnearity. This includes dose-dependent absorption, drug-drag interactions, intestinal secretion and limited access to the brain. Assays are in development to quantify the interaction between transporters and drugs. One of the first is a 96-weU plate assay for P-gp binding [33, 34] and an MDRl ATPase test [35]. 

The sponsor may wish to make specific claims in the package insert that no drug-drag interaction is expected. In these instances, the sponsor should be able to recommend specific no effect boundaries, or clinical equivalence intervals, for a drag-drag interaction. No effect boundaries define the interval within which a change in a systemic exposure measure is considered not clinically meaningful. 

Chapter 12 Drug-Drag Interactions with an Emphasis on Drag Metabolism and Transport... 

TABLE 4.7 P-gp-Mediated Drug-Drag Interactions with S 20% Change in AUC... 

Drug-drag interactions Garenoxacin An interaction of disopyramide with garenoxacin has been described [50 ]. 

Drug-drag interactions Ethanol A 50-year-old man developed intractable hypotension, which led to ischemic electrocardiographic changes and myocardial damage as a result of a disulfiram-ethanol interaction [30 ]. 

Drug-drag interactions Fluoxetine Tactile and visual hallucinations with the combination of methylphenidate and fluoxetine have been reported [77 ]. 

Drug-drag interactions Interactions with paclitaxel have been reviewed [81, 82 ]. The most important of these are pharmacodynamic interactions with other cytostatic drugs, but pharmacokinetic interactions have also been described. 

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