By Susan Kadlubar, Fred F. Kadlubar (auth.), K. Sandy Pang, A. David Rodrigues, Raimund M. Peter (eds.)
This quantity is authored via esteemed specialists within the box, and offers state-of-the artwork wisdom concerning enzyme- and transporter-based DDIs that impression the absorption and disposition of substances. It examines the categories of DDIs, methodological techniques to guage and examine DDIs mechanistically, bioinformatics, medical and toxicological results, and regulatory strategies. up to attainable, the longer term demanding situations and possibilities that lie forward are provided and mentioned. certain emphases are put on the quantitative evaluation of the jobs of alternative transporters, desire for extra particular probes and inhibitors, and popularity of extrahepatic casting off organs. destiny methods may still combine transporters and enzymes to speed up the advance of physiological based-pharmacokinetic types (PBPK-DDI) and knowledge with regards to inter-subject variability. additionally, the authors glance past small molecules and think about DDIs concerning biologic brokers, comparable to healing antibodies, that could result in pharmacologically major drug-cytokine or drug-endocrine interactions.
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Extra info for Enzyme- and Transporter-Based Drug-Drug Interactions: Progress and Future Challenges
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2008), and Zhou et al. M. Russel Fig. 1 Schematic model of the major drug transporters in enterocytes of human small intestine. SLC transporters are depicted by open circles and ABC transporters by shaded ovals. Solid arrows indicate the direction of drug transport. Dashed arrows depict the movement of driving ions. OCT1 is an electrogenic uniporter that transports organic cations (OC+ ) from blood into the cell driven by the inside-negative membrane potential. OCTN1 mediates OC+ uptake from gut lumen as a H+ /OC+ antiporter or can operate like OCTN2 as a bidirectional cation exchanger, mediating influx or efflux.
2008) Dobson and Kell (2008), Hagenbuch and Gui (2008), and Hu et al. (2008) Noe et al. (2007), Dobson and Kell (2008), Hagenbuch and Gui (2008), Hu et al. (2008), and Nies et al. (2008) Dobson and Kell (2008), Hagenbuch and Gui (2008), and Hu et al. (2008) Ho and Kim (2005), Koepsell et al. (2007), Moriyama et al. (2008), Terada and Inui (2008), and Matsushima et al. 1 (continued) 2 31 Protein MDR1/ P-glycoprotein MRP2 MRP3 ABCC2 ABCC3 ABCC family ABCB1 ABCB family Gene Primary active Primary active Primary active Mechanism Intestine Liver Kidney Intestine Liver Kidney Intestine Liver Kidney Tissue distribution BLM SM BLM (CCD) BBM CM BBM BBM CM BBM Membrane localization Vinblastine, vincristine, doxorubicin, etoposide, cisplatin, methotrexate, indinavir, ritonavir, saquinavir, grepafloxacin, glutathione conjugates, PAH Glucuronide conjugates (morphine, acetaminophen, etoposide, ethinylestradiol), methotrexate Vinblastine, vincristine, daunorubicin, doxorubicin, colchicine, docetaxel, paclitaxel, ortataxel, etoposide, imatinib, methotrexate, bisantrene, mitoxantrone, paclitaxel, topotecan, digoxin, digitoxin, celiprolol, talinolol, indinavir, nelfinavir, ritonavir, saquinavir, levofloxacin, grepafloxacin, sparfloxacin, erythromycin, ivermectin, chloroquine, amiodarone, lidocaine, losartan, lovastatin, mibefradil, fexofenadine, terfenadine, carbamazepine, desipramine, loperamide, methadone, morphine, sumatriptan, vecuronium, cyclosporin A, tacrolimus, sirolimus Examples of drug substrates Russel et al.