Abstract: The present invention relates to a pharmacokinetic-based design and selection tool (PK tool) and methods for predicting absorption of an administered compound of interest. The methods utilize the tool, and optionally a separately operable component or subsystem thereof. The PK tool includes as computer-readable components: (1) input/output system; (2) physiologic-based simulation model of one or more segments of a mammalian system of interest having one or more physiological barriers to absorption that is based on the selected route of administration; and (3) simulation engine having a differential equation solver. The invention also provides methods for optimizing as well as enabling minimal input requirements a physiologic-based simulation model for predicting in vivo absorption, and optionally one or more additional properties, from either in vitro or in vivo data.

Abstract: A carrier for in vivo delivery of a therapeutic agent comprising a thiol group is provided, wherein the therapeutic agent is conjugated to the carrier via a biodegradable disulfide bond. Since extracellular fluids in vivo do not provide the appropriate environment to efficiently reduce a disulfide bond, while cellular cytosol does provide an appropriate environment, the agent will remain substantially coupled to the carrier while circulating through the body until the carrier crosses a cell membrane. As a result, the therapeutic agent is protected from degradation and renal clearance, and the potential for the therapeutic agent to elicit an immune response is limited.

Abstract: The invention is directed to pharmaceutical compositions and methods for delivery of a therapeutic or diagnostic agent from one bodily compartment to one or more other bodily compartment by administering one of the following conjugates: a polymer having multiple functional groups at least one of which is covalently bound to a therapeutic or diagnostic agent, and at least one cell uptake promoter covalently bound to the therapeutic or diagnostic agent; or a polymer and at least one cell uptake promoter bound thereto; the polymer further comprising multiple functional groups at least one of which is covalently bound a therapeutic or diagnostic agent.

Abstract: The present invention relates to a pharmacokinetic-based design and selection tool (PK tool) and methods for predicting absorption of an administered compound of interest. The methods utilize the tool, and optionally a separately operable component or subsystem thereof. The PK tool includes as computer-readable components: (1) input/output system; (2) physiologic-based simulation model of one or more segments of a mammalian system of interest having one or more physiological barriers to absorption that is based on the selected route of administration; and (3) simulation engine having a differential equation solver: The invention also provides methods for optimizing as well as enabling minimal input requirements a physiologic-based simulation model for predicting in vivo absorption, and optionally one or more additional properties, from either in vitro or in vivo data.

Abstract: A secondary compound library produced by a method of screening a compound library or portion thereof by absorption is provided. The method includes a step (i) that screens a primary compound library or portion thereof having a plurality of test samples containing isolated compounds or isolated mixtures of compounds per test sample by generating an in vivo absorption profile for each of the test samples from initial dose data and from in vitro bioavailability data comprising permeability and solubility data for each of the test samples, wherein the absorption profile includes at least one of rate of absorption, extent of absorption, and concentration of a test sample. Step (ii) produces a secondary compound library that includes at least one compound from the primary compound library having a desired absorption profile.

Abstract: A carrier for in vivo delivery of a therapeutic agent comprising a thiol group is provided, wherein the therapeutic agent is conjugated to the carrier via a biodegradable disulfide bond. Since extracellular fluids in vivo do not provide the appropriate environment to efficiently reduce a disulfide bond, while cellular cytosol does provide an appropriate environment, the agent will remain substantially coupled to the carrier while circulating through the body until the carrier crosses a cell membrane. As a result, the therapeutic agent is protected from degradation and renal clearance, and the potential for the therapeutic agent to elicit an immune response is limited.

Abstract: The present invention relates to a pharmacokinetic-based design and selection tool (PK tool) and methods for predicting absorption of an administered compound of interest. The methods utilize the tool, and optionally a separately operable component or subsystem thereof. The PK tool includes as computer-readable components: (1) input/output system; (2) physiologic-based simulation model of one or more segments of a mammalian system of interest having one or more physiological barriers to absorption that is based on the selected route of administration; and (3) simulation engine having a differential equation solver. The invention also provides methods for optimizing as well as enabling minimal input requirements a physiologic-based simulation model for predicting in vivo absorption, and optionally one or more additional properties, from either in vitro or in vivo data.

Abstract: The present invention relates to a pharmacokinetic-based design and selection tool (PK tool) and methods for predicting absorption of an administered compound of interest. The methods utilize the tool, and optionally a separately operable component or subsystem thereof. The PK tool includes as computer-readable components: (1) input/output system; (2) physiologic-based simulation model of one or more segments of a mammalian system of interest having one or more physiological barriers to absorption that is based on the selected route of administration; and (3) simulation engine having a differential equation solver. The invention also provides methods for optimizing as well as enabling minimal input requirements a physiologic-based simulation model for predicting in vivo absorption, and optionally one or more additional properties, from either in vitro or in vivo data.

Abstract: The present invention relates to a pharmacokinetic-based design and selection tool (PK tool) and methods for predicting absorption of an administered compound of interest. The methods utilize the tool, and optionally a separately operable component or subsystem thereof. The PK tool includes as computer-readable components: (1) input/output system; (2) physiologic-based simulation model of one or more segments of a mammalian system of interest having one or more physiological barriers to absorption that is based on the selected route of administration; and (3) simulation engine having a differential equation solver. The invention also provides methods for optimizing as well as enabling minimal input requirements a physiologic-based simulation model for predicting in vivo absorption, and optionally one or more additional properties, from either in vitro or in vivo data.

Abstract: The present invention relates to a pharmacokinetic-based design and selection tool (PK tool) and methods for predicting absorption of an administered compound of interest. The methods utilize the tool, and optionally a separately operable component or subsystem thereof. The PK tool includes as computer-readable components: (1) input/output system; (2) physiologic-based simulation model of one or more segments of a mammalian system of interest having one or more physiological barriers to absorption that is based on the selected route of administration; and (3) simulation engine having a differential equation solver. The invention also provides methods for optimizing as well as enabling minimal input requirements a physiologic-based simulation model for predicting in vivo absorption, and optionally one or more additional properties, from either in vitro or in vivo data.

Abstract: A carrier for in vivo delivery of a therapeutic agent comprising a thiol group is provided, wherein the therapeutic agent is conjugated to the carrier via a biodegradable disulfide bond. Since extracellular fluids in vivo do not provide the appropriate environment to efficiently reduce a disulfide bond, while cellular cytosol does provide an appropriate environment, the agent will remain substantially coupled to the carrier while circulating through the body until the carrier crosses a cell membrane. As a result, the therapeutic agent is protected from degradation and renal clearance, and the potential for the therapeutic agent to elicit an immune response is limited.

Abstract: Proteins or peptidic substances, which may be prepared from naturally occurring proteins, enhance the bioavailability of proteolytically-labile therapeutic agents which, in the absence of the protein or peptidic substance would suffer enzymatic inactivation upon administration.