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PURPOSE To compare side-by-side the uptake of sorafenib and sunitinib in vitro by human uptake solute carriers of the SLC22A and SLCO families, the transport by and inhibition of efflux ATP-binding cassette (ABC) transporters, and the role of ABCB1 in the plasma pharmacokinetics and brain penetration of these agents. EXPERIMENTAL DESIGN Uptake of(More)
PURPOSE Many tyrosine kinase inhibitors (TKI) undergo extensive hepatic metabolism, but mechanisms of their hepatocellular uptake remain poorly understood. We hypothesized that liver uptake of TKIs is mediated by the solute carriers OATP1B1 and OATP1B3. EXPERIMENTAL DESIGN Transport of crizotinib, dasatinib, gefitinib, imatinib, nilotinib, pazopanib,(More)
PURPOSE To retrospectively evaluate the effects of six known allelic variants in the CYP2C8, CYP3A4, CYP3A5, and ABCB1 genes on the pharmacokinetics of the anticancer agent paclitaxel (Taxol). EXPERIMENTAL DESIGN A cohort of 97 Caucasian patients with cancer (median age, 57 years) received paclitaxel as an i.v. infusion (dose range, 80-225 mg/m(2)).(More)
The non-ionic surfactants Cremophor EL (CrEL; polyoxyethyleneglycerol triricinoleate 35) and polysorbate 80 (Tween) 80; polyoxyethylene-sorbitan-20-monooleate) are widely used as drug formulation vehicles, including for the taxane anticancer agents paclitaxel and docetaxel. A wealth of recent experimental data has indicated that both solubilisers are(More)
We have determined the in vitro and in vivo cellular distribution of the antineoplastic agent paclitaxel (Taxol) in human blood and the influence of Cremophor EL (CrEL), the vehicle used for i.v. drug administration. In the absence of CrEL, the blood:plasma concentration ratio was 1.07+/-0.004 (mean+/-SD). The addition of CrEL at concentrations(More)
In mice, the mdr1a and mdr1b genes encode drug-transporting proteins that can cause multidrug resistance in tumor cells by lowering intracellular drug levels. These P-glycoproteins are also found in various normal tissues such as the intestine. Because mdr1b P-glycoprotein is not detectable in the intestine, mice with a homozygously disrupted mdr1a gene(More)
2072 Background: The uridine diphosphate-glucuronsyltransferase 1A (UGT1A) family of enzymes is involved in the phase II biotransformation of various drugs, including the irinotecan metabolite, SN-38. The isoforms 1A1 and 1A9 are responsible for most of the glucuronidation of SN-38. Several genetic variants in the UGT1A9 gene have been described recently(More)
PURPOSE To provide recommendations for appropriate cytotoxic chemotherapy dosing for obese adult patients with cancer. METHODS The American Society of Clinical Oncology convened a Panel of experts in medical and gynecologic oncology, clinical pharmacology, pharmacokinetics and pharmacogenetics, and biostatistics and a patient representative. MEDLINE(More)
The purpose of the study was to determine if the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), gefitinib and erlotinib, are substrates for the efflux transporter ABCG2, and to investigate the relevance of the ABCG2 421C>A (Q141K) polymorphism to the pharmacokinetics of gefitinib. Gefitinib and erlotinib transport in vitro was(More)
Cisplatin is one of the most widely used anticancer agents for the treatment of solid tumors. The clinical use of cisplatin is associated with dose-limiting nephrotoxicity, which occurs in one-third of patients despite intensive prophylactic measures. Organic cation transporter 2 (OCT2) has been implicated in the cellular uptake of cisplatin, but its role(More)