2004
DOI: 10.1007/s00280-004-0854-6 View full text |Buy / Rent full text
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Abstract: GF120918 is an MDR converter with only minimal side effects at a dose level yielding concentrations able to convert the action of P-glycoprotein in vitro. A doxorubicin dose of 60 mg/m2 on day 3 in combination with 400 mg GF120918 twice daily on days 1-5 is an acceptable regimen for further clinical trials.

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“…Elacridar inhibited ABCG2 as well as ABCB1 and has been used in preclinical and clinical settings (38,39). Elacridar can also significantly increase plasma pharmacokinetics and brain distribution of several drugs, including dasatinib (40), gefitinib (41), and sunitinib (42).…”
Section: Discussionmentioning
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“…Elacridar inhibited ABCG2 as well as ABCB1 and has been used in preclinical and clinical settings (38,39). Elacridar can also significantly increase plasma pharmacokinetics and brain distribution of several drugs, including dasatinib (40), gefitinib (41), and sunitinib (42).…”
Section: Discussionmentioning
“…In situ single-pass jejunal perfusion and portal vein-cannulated rats were used as study systems to exclude or minimize the confounding influence of first-pass hepatic metabolism. (Planting et al, 2005), and product information is provided by Cayman Chemical (Ann Arbor, MI; www.caymanchem.com), respectively. Midazolam (MDZ) (Versed, 5 mg/ml; Roche Laboratories) was purchased through the Rutgers University Health Center Pharmacy.…”
Section: Saquinavir [Sqv (N-tert-butyl-decahydro-2-[2(r)-hydroxy-4-pmentioning
“…We also studied the reversal effects of two of the latestdeveloped potent inhibitors of human Pgp known to interact with its TMDs, namely, zosuquidar (LY335979) (8,9) and elacridar (GF120918) (20,40). In contrast to other modulators of mammalian Pgp, both compounds were quite active in reversing DNM resistance in the MDR Leishmania line, elacridar being more toxic for the parental wild-type line (Fig.…”
Section: Resultsmentioning
“…This interaction at the TMDs, however, does not seem to lead to transport of the compound. We also analyzed the reversing effect of some new modulators of human Pgp that are known to interact with its TMDs and not to be transported (8,9,20,40). While conventional Pgp inhibitors such as verapamil, cyclosporine, and quinidine were not very efficient at reversing the resistance phenotype in Leishmania (35), we show here that the latestdeveloped modulators zosuquidar (LY335979) and elacridar (GF120918) constitute new classes of promising reversal agents in these parasites.…”
Section: Discussionmentioning
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