Drug transport mechanisms

Fig. 4.4. A current trend in drug transport studies is to use simplified cell models that facilitate the characterisation of selected drug transport mechanisms. However, recent research suggests that such simplified systems are not useful in cases where two or more drug transporters act in synergy. Development of cell models for such complex transport mechanisms will require the technically...

Drug Transport Mechanisms TABLE 14.2 Sample of QSAR Studies on TTansport ... 

Apart from these basic rules of thumb, the ability to predict the relationship between molecular structure and transport across biological membranes is limited beyond narrow ranges of known compounds. Confounding factors include inaccurate, incomplete, and/or noncomparable data, and the potential existence of multiple drug transport mechanisms in real biological membranes. In particular, limited QSAR data are available for the specific drug transporters that are considered in the following sections. 

In eight patients a single 500 mg oral dose of azithromycin was not substantially removed by continuous ambulatory peritoneal dialysis in the absence of peritonitis. Azithromycin cannot be recommended for widespread use in CAPD at present. However, the successful use of azithromycin in treating peritonitis, perhaps because of an intracellular drug transport mechanism, has been reported (44). 

ZD0473 (formerly AMD473, JM473) was developed in order to overcome acquired or intrinsic (de novo) resistance to cisplatin. Based on the steric bnlk of its methyl-substituted pyridine moiety, thiol snbstitntion and drug inactivation is hindered compared with cisplatin. In several in-vitro studies, ZD0473 was active even in cisplatin-refractory tumor cells, whose key mechanism of resistance was based on thiol substitution. In addition, ZD0473 is also active in cisplatin-resistant tumor cells, in which resistance is based on altered drug transport mechanisms or enhanced DNA repair. 

Drug Transport Mechanisms and their Impact on the Disposition and Effects of Drugs... 

As a drug is distributed in the body, it comes in contact with numerous membranes. Drugs pass some membranes but not others. Table 1.2 compares four drug transport mechanisms. 

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