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The U.S. Food and Drug administration (FDA) has approved several polyclonal antibody preparations and at least 18 monoclonal antibody preparations (antibodies, antibody fragments, antibody fusion proteins, etc.). These drugs, which may be considered as a diverse group of therapeutic proteins, are associated with several interesting pharmacokinetic(More)
It has been suggested that the neonatal Fc receptor (FcRn) is a primary determinant of the distribution of IgG to the brain. In the present report, (125)I-labeled 7E3, a monoclonal IgG1 antibody, was injected intravenously to groups of FcRn-deficient mice and C57BL/6J control mice. Sub-groups of three mice were sacrificed at several time points. Blood and(More)
Recently, our laboratory reported that intravenous immunoglobulin (IVIG) treatment increased antiplatelet antibody (7E3) clearance in a rat model of immune thrombocytopenic purpura (ITP). However, due to the multifaceted nature of IVIG therapy, the contribution of this increase in antiplatelet antibody clearance to the total therapeutic effect of IVIG was(More)
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(More)
Accurate prediction of the clinical pharmacokinetics of new therapeutic entities facilitates decision making during drug discovery, and increases the probability of success for early clinical trials. Standard strategies employed for predicting the pharmacokinetics of small-molecule drugs (e.g., allometric scaling) are often not useful for predicting the(More)
More than 20 monoclonal antibodies have been approved as therapeutic drugs by the US Food and Drug Administration, and it is quite likely that the number of approved antibodies will double in the next 7-10 years. Antibody drugs show several desirable characteristics, including good solubility and stability, long persistence in the body, high selectivity and(More)
Although it is known that FcRn, the neonatal Fc-receptor, functions to protect immune gamma globulin (IgG) from elimination, the influence of FcRn on the tissue distribution of IgG has not been quantified. In the present work, a physiologically-based pharmacokinetic (PBPK) model has been developed to characterize and predict IgG disposition in plasma and in(More)
Antibodies directed against tumor associated antigens are being increasingly used for detection and treatment of cancers; however, there is an incomplete understanding of the physiological determinants of antibody pharmacokinetics and tumor distribution. The purpose of this study is to (a) compare the plasma pharmacokinetics of T84.66, a monoclonal anti-CEA(More)
The time course of chemotherapeutic effect is often delayed relative to the time course of chemotherapeutic exposure. In many cases, this delay is difficult to characterize mathematically through the use of standard pharmacodynamic models. In the present work, we investigated the relationship between methotrexate (MTX) exposure and the time course of MTX(More)
The objective of this study was to investigate the pharmacokinetics and toxicodynamics of topotecan (TPT) in mice and to develop an integrated pharmacokinetic/toxicodynamic (PK/TD) model to characterize the relationship between the time course of TPT disposition and the time course of TPT-induced toxicity. TPT was administered to groups of 3-5 mice via i.v.(More)