Possible Mechanisms of Interaction

In addition to CYP3A4, enterocyte efflux transport proteins such as P-gp, and enterocyte uptake proteins, such as OATPs also appear to be involved in grapefruit rug interactions (24,72). The activity of P-gp has been reported to be altered by GFJ and orange juice in in vitro experiments (73,74), whereas the clinical relevance currently seems unclear, as demonstrated by inconsistent results from human clinical trials (22,75 77). 

Regarding interactions between citrus and OATP, data from in vitro, animal and also human clinical studies are available. These studies demonstrated the inhibition of OATP-A in HeLa cells and of OATP-B mediated uptake of estrone-3-sulfate in human embryonic kidney cells and also in the oral intake of fexofenadine in rats by fruit juices, including GFJ and orange juice. Human clinical trials suggest a potential role of OATP in grapefruit-drug interactions using fexofenadine as substrate (22,23,67,78,79). 

Clinical studies that compare the effects of orange juice with GFJ on drug bioavailability confirm the involvement of P-gp in grapefruit-induced 

Several in vitro studies with different probes (talinolol, digoxin, and vinblastine) also confirm the findings that GFJ inhibits the efflux of P-gp substrates (20,54,73). 

In addition to GFJ, orange juice and pomelo juice also have been shown to inhibit the activity of P-gp in vitro (73). Flavones from orange juice have been shown to be more potent than compounds from grapefruit in the inhibition of P-gp (97). 

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These considerations lead us to a conclusion that nerve excitation is a very slow process and the membrane does not contain elements which has a frequency response of MHz or GHz. The only molecular species which may have such a frequency response are water molecules. However, the role of water in nerve excitation is totally unknown and does not offer, at present, any evidence for the possible mechanism of interaction between micro-waves and nerve membranes. 

At present there is consensus on the fact that the observed nephelauxetic effect in the spectra of lanthanide compounds is analogous to the phenomenon observed in the spectra of d-transition metal complexes. The nephelauxetic effect cannot be quantitatively interpreted by excluding the covalent interaction of lanthanide ions with surrounding ligands [34]. Jorgensen has proposed [38] two possible mechanisms of interaction for the observed nephelauxetic effect, namely (i) direct participation of lanthanide 4f orbitals in the formation of molecular orbitals also known as symmetry restricted covalency , (ii) transfer of some part of the ligand electron density to the unfilled 6s and 6p orbitals of the lanthanide also known as central field covalency . 

Bigal ME, KurthT, HuH,SantaneUoN, LiptonRB Migraine and cardiovascular disease possible mechanisms of interaction. Neurology 2009 72 pp. 1864-1871. 

Patients with hypothyroidism and organic depression may need both levothyroxine and antidepressant drug therapy, in ievothyroxine-treated patients with hypothyroidism who were treated with sertraiine, there was an eievated serum thyrotropin concentration, indicative of a decrease in the efficacy of ievothyroxine. What is the possible mechanism of interaction between the two drugs ... 

Russo ME. Penicillin-aminc ycoside inactivaticn another possible mechanic of interaction. Pharm (1980) 37,702-. ... 

The possible mechanisms of interaction of the positronium atoms are as follows ... 

Sz4zdi, L., Pukanszky, B. Jr., Foldes, E., and Pukanszky, B. Jr. 2005. Possible mechanism of interaction among the components in MAPP modified layered silicate PP nanocomposites. Polymer 46 8001-8010. 

Naganuma et al., 1980). Selenide has been found to react with methyl-mercury in vitro to form bis(methylmercuric)selenide (reaction 10), but either protein sulfhydryl groups or reduced glutathione was needed when other chemical forms of selenium were used (Iwata et al., 1981). The detection of selenide, although at very low levels, in the tissues of mice treated with selenium and methylmercury (Naganuma et al., 1980) is evidence that this reaction occurs in animals. Hence, there are several possible mechanisms of interaction of selenium with cadmium, mercury, and silver, and many physiological aspects of this interaction still to be elucidated. 

Figure 5.6b represents two possible mechanisms of interaction between dopamine and acetylcholine. Inhibitory dopaminergic ami excitatory cholinergic neurons either synapse onto the same striatal neuron, or there is an intermediary cholinergic interneuron in the striatum... 

Fig. 5 Schematic representation for the possible mechanism of interactions between cationic surfactant and charged oxide surface ...

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