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Biodistribution and Pharmacokinetics of EGFR-targeted Thiolated Gelatin Nanoparticles Following Systemic Administration in Pancreatic Tumor-bearing Mice

The objective of this study was to evaluate qualitative and quantitative biodistribution of epidermal growth factor receptor (EGFR)-targeted thiolated type B gelatin nanoparticles in vivo in subcutaneous human pancreatic adenocarcinoma (Panc-1) bearing female SCID Beige mice. EGFR-targeted nanoparticles showed preferential and sustained accumulation in the tumor mass, especially at early time points. Higher blood concentrations … Continued

Investigation of the Role of Fc-γ-R and FcRn in mAb Distribution to the Brain

To evaluate the role of Fc receptors (FcR) on IgG distribution to the brain, the disposition of 8C2, a murine monoclonal IgG1 antibody, was investigated after intravenous administration in FcRn α-chain knockout mice, FcγRIIb knockout mice, FcγRI/RIII knockout mice, and C57BL/6 control mice. (125)I-8C2 was co-administered with (51)Cr-labeled red blood cells to allow accurate assessment of residual blood content in brain samples. Blood and brain … Continued

Brain Extracellular γ-hydroxybutyrate Concentrations are Decreased by L-lactate in Rats: Role in the Treatment of Overdoses

L-lactate represents a potential treatment for GHB overdose by inhibiting GHB renal reabsorption mediated by monocarboxylate transporters. Our objective was to assess the dose-dependence of L-lactate treatment, with and without D-mannitol, on GHB toxicokinetics/toxicodynamics (TK/TD). Rats were administered GHB 600 mg/kg i.v. with L-lactate (low and high doses), D-mannitol, or L-lactate (low dose) with D-mannitol. GHB-induced … Continued

Physiologically-based Pharmacokinetic Models for Everolimus and Sorafenib in Mice

Everolimus is a mammalian target of rapamycin (mTOR) inhibitor approved as an immunosuppressant and for second-line therapy of hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC). Sorafenib is a multikinase inhibitor used as first-line therapy in HCC and RCC. This study assessed the pharmacokinetics (PK) of everolimus and sorafenib alone and in combination in plasma … Continued

Synergistic Interactions between Sorafenib and Everolimus in Pancreatic Cancer Xenografts in Mice

Molecular targeting of cellular signaling pathways is a promising approach in cancer therapy, but often fails to achieve sustained benefit because of the activation of collateral cancer cell survival and proliferation pathways. We tested the hypothesis that a combination of targeted agents that inhibit compensatory pathways would be more effective than single agents in controlling … Continued

Do Children Have the Same Vulnerability to Metabolic Drug-drug Interactions as Adults? A Critical Analysis of the Literature

Many drug–drug interactions (DDIs) in the pediatric population are managed based on data generated in adults. However, due to developmental changes in elimination pathways from birth to adolescence, and variable weight-adjusted dose of interacting drugs, the assumption of DDIs being similar in adults and pediatrics might not be correct. This study compares the magnitude of … Continued

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