公开(公告)号：EP1185948B1

公开(公告)日：2006-03-01

申请号：EP99948226.8

申请日：1999-09-14

申请人： Lion bioscience AG

发明人： GRASS, George M. ,  LEESMAN, Glen, D. ,  NORRIS, Daniel, A. ,  SINKO, Patrick, J. ,  WEHRLI, John, E.

IPC分类号： G06F19/00 ,  C12Q1/00

CPC分类号： C40B30/02 ,  C40B50/02 ,  Y02A90/26

摘要： 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. The PK tool of the invention may be provided as a computer system, as an article of manufacture in the form of a computer-readable medium, or a computer program product and the like. Subsystems and individual components of the PK tool also can be utilized and adapted in a variety of disparate applications for predicting the fate of an administered compound. The PK tool and methods of the invention can be used to screen and design compound libraries, select and design drugs, as well as predict drug efficacy in mammals from in vitro and/or in vivo data of one or more compounds of interest. The PK tool and methods of the invention also finds use in selecting, designing, and preparing drug compounds, and multi-compound drugs and drug formulations (i.e., drug delivery system) for preparation of medicaments for use in treating mammalian disorders.

公开(公告)号：EP1386274A2

公开(公告)日：2004-02-04

申请号：EP01956037.4

申请日：2001-07-30

申请人： LION bioscience AG

发明人： LEESMAN, Glen, D. ,  NORRIS, Daniel, A. ,  SINKO, Patrick, J. ,  HOLME, Kevin ,  IZHIKEVICH, Tatyana ,  DOERR-STEVENS, Julie ,  LECLUYSE, Edward ,  THAKKER, Dhiren, R. ,  GRASS, George, M.

IPC分类号： G06F19/00

CPC分类号： G06F19/704 ,  G06F19/00 ,  G16H10/40 ,  G16H50/50

摘要： A system for simulating metabolism of a compound in a mammal is disclosed that includes a metabolism simulation model of a mammalian liver. This model has equations which when executed on a computer, calculate the rate of metabolism of the compound in the cells of the mammalian liver and a rate of transport of the compound into the cells, wherein the simulation model determines an amount of the metabolism product. The rate of metabolism may be a rate of depletion of the compound. The metabolism product may be an amount of the compound remaining after the compound's first passage through the mammalian liver (This is not necessarily limited to first pass, nor would it need to be limited to the liver. Intestinal metabolism could also be modeled). The rate of metabolism may alternatively be a rate of accumulation of a metabolite of the compound.

公开(公告)号：EP1358612A2

公开(公告)日：2003-11-05

申请号：EP01957310.4

申请日：2001-07-30

申请人： LION bioscience AG

发明人： GRASS, George, M. ,  LEESMAN, Glen, D. ,  NORRIS, Daniel, A. ,  SINKO, Patrick, J. ,  ATHWAL, Jehangir ,  SAGE, Carleton ,  BREMER, Troy ,  HOLME, Kevin ,  YONG, Lee ,  LEE, Kyoung

IPC分类号： G06F19/00

CPC分类号： G06F19/704 ,  G06F19/00 ,  G06F19/707 ,  G16H10/40 ,  G16H50/50

摘要： Permeability models and methods for creating the models are disclosed. The models include receiving as an input in vitro permeability and structure data for a particular compound. Then the data is mapped to at least one permeability. In some models the data is mapped to a plurality of permeabilities, each associated with a specific region in a mammalian GI tract. Some models may take into consideration solubility, permeability and at least one molecular descriptor associated with the compound of interest.