Transporter drugs modulating functions

The modes of action of these drugs are still uncertain, but it seems likely that there are antiinflammatory and antienzyme activities of gold(I) compounds. It may be that the drugs modulate the body s immune response in some way. Unlike iron and copper, which are essential elements, gold does not have a well-defined transport, storage or enzyme function.17... 

Limtraknl, P. et al.. Modulation of the function of three ABC drug transporters, P-glycoprotein (ABCBl), mitoxantrone resistance protein (ABCG2) and multidrug resistance protein 1 (ABCCl) by tetrahydroenrenmin, a major metabolite of cur-enmin. Mol. Cell Biochem., 296, 85, 2007. 

Ion transport processes of the cornea and the conjunctiva can play an important role in maintaining intra- and extracellular fluid homeostasis, signal transduction, and intercellular communication. As all these functions may contribute to the modulation of drug transport (see Section IV.B), it is essential that the baseline ion transport processes in the cornea and the conjunctiva be understood. 

Breast Cancer Resistance Protein (BCRP, also known as MXR or ABCP), first cloned from mitoxantrone and anthracycline-resistant breast and colon cancer cells [188, 189] is a half-transporter efflux pump believed to function as a homo-or hetero-dimer. Following its identification, BCRP-mediated drug resistance was observed for topoisomerase inhibitors including camptothecins [190, 191] and in-dolocarbazoles [192]. In normal tissues, BCRP was detected in placental syncytio-trophoblasts, hepatocyte canalicular membrane, apical intestinal epithelia and vascular endothelial cells [193]. These findings support the important role BCRP plays in modulating topotecan bioavailability, fetal exposure and hepatic elimination [194]. Considering that the substrates and tissue distributions for BCRP overlap somewhat with MDR1 and MRPs [195], additional studies will be required to define the relative contribution of each of these transporters in the overall and tis-... 

Powell, D.W., Barrier function of epithelia. Am. J. Physiol., 241 G275-G288 (1981). Nellans, H.N., Paracellular intestinal transport modulation of absorption, Adv. Drug Del. Rev., 7 339-364 (1991). 

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. 

The stratum corneum basically contains a mixture of cholesterol, free fatty acids, and ceramides, placed in multilayers. They mediate both the epidermal permeability barrier and the transdermal delivery of both lipophilic and hydrophilic molecules. Studies have shown that each of the three key lipid classes is required for normal barrier function (32). These reports also show the potential of certain inhibitors of lipid synthesis to enhance the trans-dermal delivery of drugs like lido-caine or caffeine. Thus, the modulation of stratum corneum lipids is an important determinant of the barrier permeability to both hydrophobic and hydrophilic compounds transport and drug penetration. It has been reported that an inverse correlation exists between solute penetration and stratum corneum lipid content (33). 

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