Rat IgG1 kappa Isotype Control [eFluor® 450]

Background and Objectives ABT-806 is a veneered 'humanized' recombinant IgG1 kappa antibody that is specific for a unique epitope of human epidermal growth factor receptor (EGFR) expressed only on tumor cells with the EGFRde2-7 (EGFRvIII) deletion mutant as well as tumors with wild-type amplified receptors. We aimed to develop a population pharmacokinetic model of ABT-806 in cancer patients, and to evaluate fixed versus body weight-based dosing regimens. Methods The pharmacokinetics of ABT-806 were evaluated in a phase I, open-label study in cancer patients following intravenous infusion of ABT-806 every other week. A total of 587 serum concentrations of ABT-806 from 61 patients were analyzed using non-linear mixed-effects modeling. The impact of body weight-based and fixed dosing of ABT-806 was evaluated using a simulation approach. Results A two-compartment model with linear elimination was used to describe the serum concentration-time data of ABT-806. The population estimates of the apparent clearance from the central (CLc) and peripheral (CLp) compartments were 0.011 and 0.025 L/h, respectively. The apparent volume of distribution estimates of the central (V-1) and peripheral (V-2) compartments were 3.5 and 3.3 L, respectively. The estimates of inter-subject variability (percentage coefficient of variation) in CLc, CLp, V-1, and V-2 were 38, 37, 20, and 48 %, respectively. Albumin on CLc and body weight on V-1 were statistically significant covariates; however, they explained 18 and 30 % of the inter-individual variability of clearance and V-1, respectively. Simulation results indicated that fixed and body weight-based dosing regimens yield similar steady-state concentrations and overall variability. Conclusions ABT-806 demonstrated a unique pharmacokinetic profile compared to the marketed monoclonal antibodies against EGFR. The analysis indicates it is feasible to switch to fixed doses in subsequent clinical trials of ABT-806.

Recent study reports that Korean red ginseng reduces the nasal allergic inflammatory reaction in an allergic murine model. However, the contribution of ginsenoside Rg1 (RG1) and its mechanisms on allergic rhinitis (AR) have not been elucidated. In this study, we evaluated the important activities of RG1 in the ovalbumin (OVA)-induced AR mice. RG1 significantly reduced the levels of thymic stromal lymphopoietin (TSLP) and interleukin (IL)-1 beta compared with the AR control mice. Allergic symptom such as rub scores and biomarkers such as spleen weight, histamine, IgE and IgG1 in the RG1 group were decreased compared with the AR mice. The levels of interferon-g were enhanced while the levels of IL-4 were reduced in the RG1 group. In the RG1 group, the eosinophils and mast cells infiltration increased by OVA were also decreased. RG1 reduced the levels of inflammation-related protein. RG1 inhibited the caspase-1 activity in nasal mucosa tissue. In addition, RG1 inhibited the production of TSLP and IL-1 beta and the activations of caspase-1, receptor interacting protein 2, I kappa B kinase-beta and nuclear factor-kappa B/Rel A in activated HMC-1 cells. Our results indicate that RG1 has the inhibitory effect of TSLP production and caspase-1 activity in AR experimental model.