Alain Dauphin

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BACKGROUND Identifying predictive biomarkers of drug response is of key importance to improve therapy management and drug selection in cancer therapy. To date, the influence of drug exposure and pharmacogenetic variants on sorafenib-induced toxicity remains poorly documented. The aim of this pharmacokinetic/pharmacodynamic (PK/PD) study was to investigate(More)
BACKGROUND Sunitinib malate is a novel oral multitargeted tyrosine kinase inhibitor with antitumor and antiangiogenic activities. Only mass spectrometry detection is currently available to determine sunitinib in human plasma. The purpose of this study was to develop a simple and sensitive high-performance liquid chromatographic method with UV-Visible(More)
Sorafenib, an orally active multi–kinase inhibitor approved for the treatment of hepatocellular carcinoma (HCC), is primarily metabolized both via cytochrome P450 3A4 isoform (CYP3A4) and UGT1A9. Due to the contribution of these two biotransformation pathways, sorafenib is considered to be less susceptible than other agents to CYP3A4 drug–drug interactions.(More)
Mycophenolate mofetil (MMF) pharmacokinetics variability in liver transplant recipients during the early posttransplantation period may be related to changes in mycophenolic acid (MPA) protein binding. This study aimed at characterizing the variation of free MPA exposure with respect to time since transplantation. Three groups (A, B, C) were compared. The(More)
Sorafenib is an oral tyrosine kinase inhibitor approved for the treatment of advanced renal cell carcinoma and hepatocellular carcinoma. By using a population approach, this study aimed to characterise its pharmacokinetics. Plasma concentration-time data (n = 372) from 71 patients under sorafenib were analysed using nonlinear mixed-effect modelling to(More)
Gefitinib and erlotinib are two oral tyrosine kinase inhibitors (TKI) approved for the treatment of advanced non-small cell lung cancer (NSCLC). Published methods for simultaneous analysis of erlotinib and gefitinib in plasma are exclusively based on mass spectrometry. The purpose of this study was to develop a simple and sensitive HPLC-UV method to(More)
Sorafenib, an oral multitargeted tyrosine kinase inhibitor, is highly bound to plasma proteins (>99.5%). Little is known about the influence of variations in sorafenib protein binding on its disposition. The aims of this study were to characterize in vitro sorafenib binding properties to albumin using the quenching fluorescence method and investigate the(More)
Mycophenolic acid (MPA) is 98-99% bound to albumin. Because MPA is restrictively cleared and has a low extraction coefficient, increase in its free fraction related to decreased albumin binding results in lower total concentrations but unchanged unbound concentrations. Multiple factors, including hypoalbuminemia, impaired renal function, and accumulated(More)
Although selective 5-HT reuptake inhibitors (SSRIs) block monoamine uptake within hours of administration to patients, their full clinical effect does not appear until 2–4 weeks after treatment onset. Pindolol, a betablocker with weak partial 5-HT1A receptor agonist activity has been shown to produce a more rapid onset of antidepressant action of SSRIs.(More)
Immunotherapy is a promising antitumor strategy that can successfully be combined with current anticancer treatment. In this study, arsenic trioxide (As(2)O(3)) was shown to increase the antitumor immune response in CT26 colon tumor-bearing mice through the modulation of regulatory T cell (T(reg)) numbers. As(2)O(3) induced T(reg)-selective depletion in(More)