Nuclear Receptors in Drug Metabolism by Wen Xie

By Wen Xie

This ebook delivers an up to date and specialist review of nuclear hormone receptors in drug metabolism and drug improvement and equips you with the interdisciplinary realizing of those receptors and the way they are often regulated. Pharmaceutical researchers will locate this super necessary in constructing medicines for melanoma, center disorder, and diabetes therapy. This accomplished source collects scattered fabrics into one convenient, informative quantity.

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It is also expressed in other tissues such as the kidney, as well as the intestinal entrocytes [97, 98] and apical membrane of brain capillary endothelial cells [99]. In humans, a genetic deficiency of MRP2 results in a disease known as Dubin–Johnson syndrome [100]. In addition, altered MRP2 function can change the ADME properties of many clinically important drugs including cancer chemotherapeutics (irinotecan, methotrexate, and vinblastine), antibiotics (ampicillin and rifampin), antihyperlipidemics, and angiotensin-converting enzyme inhibitors.

Clinical studies on renal transplant patients showed that grapefruit juice significantly enhanced the systemic exposure of cyclosporine, while having no significant effects on prednisone or prednisolone [137]. Further investigations have established that the effect is on drugs that are primarily cleared by CYP3A4 and show low bioavailability due to presystemic metabolism by CYP3A4 P1: PIC/PIC P2: ABC c01 JWBK262/Xie September 18, 2008 18:59 Printer Name: Yet to Come CHALLENGES IN DRUG METABOLISM 19 in the entrocytes.

2 In Vitro–In Vivo Extrapolation. 0-fold variation) is an ongoing challenge with many different approaches yielding varying degrees of success. Interspecies allometric scaling of pharmacokinetic parameters is the earliest of the approaches and is still a tool used in predicting human pharmacokinetic behavior of drugs. The method is based on empirically observed relationships between physiological processes and body weights of mammals [115]. Several enhancements have been introduced to the original method such as maximum life-span potential, brain weight, body surface area, rule of exponents, and protein binding [115–117].

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