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Recent studies indicate that the pharmaceutical fluoxetine, a selective serotonin reuptake inhibitor, is discharged in municipal wastewater treatment plant effluents to surface waters. Few data on environmental fluoxetine exposure and hazard to aquatic life are currently available in the literature. Here, we summarize information on fluoxetine detection in(More)
Ecological risk assessments of pharmaceuticals are currently difficult because little-to-no aquatic hazard and exposure information exists in the peer-reviewed literature for most therapeutics. Recently several studies have identified fluoxetine, a widely prescribed antidepressant, in municipal effluents. To evaluate the potential aquatic toxicity of(More)
To confirm the safety and tolerability, evaluate the pharmacokinetics (PK), and investigate the antitumor activity of abemaciclib in Japanese patients with advanced cancer. We conducted a non-randomized, single-arm, open-label, dose-escalation phase 1 study of abemaciclib administered orally every 12 h (Q12H) on a 28-day cycle at doses of 100 mg (Cohort 1,(More)
Although pharmaceuticals are increasingly found in surface waters, environmental levels of many of these compounds are not acutely toxic to model test organisms. Prior to conducting appropriate ecological risk assessments of pharmaceuticals, the mode of action-based biomarkers needs to be developed for non-target species. To evaluate toxicity of the(More)
BACKGROUND Tasisulam sodium (hereafter referred to as tasisulam) is a novel, highly albumin-bound agent that demonstrated activity in a phase 2 melanoma study. METHODS In this open-label phase 3 study, patients with AJCC stage IV melanoma received tasisulam (targeting an albumin-corrected exposure of 1200-6400 h (hour).μg/mL on day 1) or paclitaxel (80(More)
Potentiation of 5-fluorouracil/leucovorin (FUra/LV) cytotoxicity by IFN-gamma in colon carcinoma cells is dependent on FUra-induced DNA damage, the Fas death receptor, and independent of p53 and RNA-mediated FUra toxicity, which occurs in normal gastrointestinal tissues. This provides a rationale for enhancing the selective action of FUra/LV by IFN-gamma in(More)
Purpose: To develop and validate a pharmacokinetic limited sampling model (LSM) for intravenous and oral topotecan pharmacokinetic studies in children. Methods: Topotecan lactone concentration-time data from five trials were used to develop and validate LSM for intravenous and oral topotecan. Based on full sampling from one intravenous study (30 patients;(More)
Increased insight into the mechanism of interaction of topoisomerase I interactive agents will maximize the therapeutic index and enhance the development of additional agents. Preclinical studies designed to elucidate mechanisms by which the topoisomerase I interactive agents induce cell death will be essential. The role of ABC transporters in resistance to(More)
The study objectives were to define subcutaneous (s.c.) interferon gamma (IFN-γ) disposition in patients with gastrointestinal malignancies receiving 5-fluorouracil (5-FU) and leucovorin (LV) and to examine the relationship between IFN-γ exposures and Fas upregulation in vivo and in vitro. Patients received IFN-γ (10, 25, 50, 75, and 100 μg/m2) with LV and(More)
This phase I study was designed to determine the maximum tolerated dose (MTD) and the dose to be recommended for a future phase II study of tasisulam sodium in Japanese patients with advanced, refractory solid tumors. Safety, pharmacokinetics and preliminary anti-tumor activities were assessed. Due to high-affinity albumin binding, an albumin-tailored dose(More)