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• W2035471279 abstract "The YSNSG peptide is a synthetic peptide targeting αvβ3 integrin. This peptide exhibits promising activity in vitro and in vivo against melanoma. To determine pharmacokinetic parameters and predictive active doses in the central nervous system (CNS) and subcutaneous tissue (SC), we conducted microdialysis coupled with pharmacokinetic modeling and Monte Carlo simulation. After a recovery period of surgical procedures, a microdialysis probe was inserted in the caudate and in subcutaneous tissue. Plasma samples and dialysates collected 5 h after YSNSG intravenous administration (10 mg/kg) were analyzed by UPLC-MS/MS. A nonlinear mixed-effect modeling approach implemented in Monolix® 2016R1 was performed. Model selection and evaluation were based on the usual diagnostic plot, precision and information criteria. The primary plasma and tissue pharmacokinetic parameters were comparable with those of other integrin antagonists, such as cilengitide or ATN-161. Tissue/plasma and brain/plasma area under the curve (AUC) ratio were 66.2 ± 21.6% and 3.6 ± 4.7%, respectively. Two models of 2-compartments with an additional microdialysis compartment, parameterized as rate constants (k for elimination, k12/k21 and k13/k31 for distribution) and volumes (central V1 and peripheral microdialysis compartment V3) with zero-order input were selected to describe the dialysate concentrations in CNS and SC. The inter-individual variability (IIV) was described by exponential terms, and residual variability was described by a combined additive and proportional error model. Individual AUC (plasma and tissues) values were derived for each animal using the Empirical-Bayes-Estimates of the individual parameters. The regimens needed to achieve an in vitro predetermined target concentration in tissues were studied by Monte Carlo simulations using Monolix® 2016R1. YSNSG pharmacokinetic parameters show promising results in terms of subcutaneous disposition. Further investigations into such processes as encapsulation and intratumoral disposition are currently being conducted." @default.
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• W2035471279 date "2008-10-01" @default.
• W2035471279 modified "2023-09-26" @default.
• W2035471279 title "419 POSTER A phase I safety and pharmacokinetic (PK) study of 3 and 6 hours (h) intravenously administered belinostat (PXD101) plus carboplatin (C) and paclitaxel (P) in patients (pts) with advanced solid tumours" @default.
• W2035471279 doi "https://doi.org/10.1016/s1359-6349(08)72353-x" @default.
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