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The primary purpose of this study was to evaluate the effect of CYP2C8*3 and three genetic ABCB1 variants on the elimination of paclitaxel. We studied 93 Caucasian women with ovarian cancer treated with paclitaxel and carboplatin. Using sparse sampling and nonlinear mixed effects modeling, the individual clearance of unbound paclitaxel was estimated from(More)
PURPOSE Docetaxel is extensively metabolized by CYP3A4 in the liver but mechanisms by which the drug is taken up into hepatocytes remain poorly understood. We hypothesized that (i) liver uptake of docetaxel is mediated by the polymorphic solute carriers OATP1B1 and OATP1B3 and (ii) inherited genetic defects in this process may impair systemic drug(More)
A major problem in the treatment of schizophrenic patients with current antipsychotic drugs, mainly acting as dopamine-2 receptor antagonists, is the occurrence of side effects such as extrapyramidal symptoms (EPS). Meta-analyses of summary data of EPS occurrence, and receptor occupancies inferred from mean plasma concentrations, have shown the incidence of(More)
Modeling and simulation were utilized to characterize the efficacy dose response of sublingual asenapine in patients with schizophrenia and to understand the outcomes of six placebo-controlled trials in which placebo responses and dropout rates varied. The time course of total Positive and Negative Syndrome Scale (PANSS) scores was characterized for placebo(More)
Pharmacokinetic-pharmacodynamic (PKPD) modeling and simulation has evolved as an important tool for rational drug development and drug use, where developed models characterize both the typical trends in the data and quantify the variability in relationships between dose, concentration, and desired effects and side effects. In parallel, rapid emergence of(More)
Trastuzumab emtansine (T-DM1) is an antibody–drug conjugate (ADC) therapeutic for treatment of human epidermal growth factor receptor 2 (HER2)-positive cancers. The T-DM1 dose product contains a mixture of drug-to-antibody ratio (DAR) moieties whereby the small molecule DM1 is chemically conjugated to trastuzumab antibody. The pharmacokinetics (PK)(More)
Population modeling of tumor size dynamics has recently emerged as an important tool in pharmacometric research. A series of new mixed-effects models have been reported recently, and we present herein a synthetic view of models with published mathematical equations aimed at describing the dynamics of tumor size in cancer patients following anticancer drug(More)
The predictive value of longitudinal biomarker data (vascular endothelial growth factor (VEGF), soluble VEGF receptor (sVEGFR)-2, sVEGFR-3, and soluble stem cell factor receptor (sKIT)) for tumor response and survival was assessed based on data from 303 patients with imatinib-resistant gastrointestinal stromal tumors (GIST) receiving sunitinib and/or(More)
PURPOSE To characterize the population pharmacokinetics of bevacizumab, its binding properties to VEGF165 and the effect of demographic data and VEGF-A polymorphisms on the interplay between bevacizumab serum pharmacokinetics and VEGF165 serum concentrations in patients with colorectal cancer stage IV. METHODS Bevacizumab and VEGF165 data were collected(More)
Our objective was to examine the evidence of in vitro synergy of polymyxin-carbapenem combination therapy against Gram-negative bacteria (GNB). A systematic review and meta-analysis were performed. All studies examining in vitro interactions of antibiotic combinations consisting of any carbapenem with colistin or polymyxin B against any GNB were used. A(More)