公开(公告)号：WO2003079004A3

公开(公告)日：2003-09-25

申请号：PCT/EP2003/002689

申请日：2003-03-14

申请人： PHARMACIA ITALIA S.P.A. ,  UNIVERSITA' DEGLI STUDI DI PAVIA ,  CAMMIA, Cristiano ,  DE NICOLAO, Giuseppe ,  POGGESI, Italo ,  ROCCHETTI, Maurizio

发明人： CAMMIA, Cristiano ,  DE NICOLAO, Giuseppe ,  POGGESI, Italo ,  ROCCHETTI, Maurizio

IPC分类号： G06F19/00

摘要： The present invention relates to a method for estimating or predicting the anti-tumor activity of a compound and for estimating or predicting the tumor growth in mammals; the estimation of the anti-tumor activity of a compound administered to mammals developing a tumor comprises a) measuring the tumor weight in time; b) measuring the concentration of the compound in time; c) calculating, on the basis of said measures, the following kinetic parameters of the tumor growth: a parameter (L 0 ), representative of the portion of the tumor cells present at the instant t 0 =0 that succeeds in taking root and in starting the tumor cells proliferation in the mammals; an index (λ O ) of the production rate of the tumor cells during an exponential phase of the tumor growth; -an index (λ 1 ) of the tumor cells mass produced in the time unit during a linear phase of the tumor growth; and the following pharmacodynamic parameters of the compound: an index (K 1 ) of the tumor cells death rate; an index (K 2 ) of the potency of the compound; and d) calculating, on the basis of said kinetic and pharmacodynamic parameters, tumor growth curves. The invention, applicable in the pharmaceutical field, allows to make the best use of all the information generated during the preclinical studies and results to be sufficiently simple also allowing to get good estimates or predictions regardless of the uncertainties on the mode of action. The invention further allows to employ a small number of parameters, therefore avoiding time consumption as well as a number of mechanistic observations.

公开(公告)号：WO0175639A3

公开(公告)日：2002-10-10

申请号：PCT/EP0103252

申请日：2001-03-22

申请人： PHARMACIA ITALIA SPA ,  BELLAZZI RICCARDO ,  DE NICOLAO GIUSEPPE ,  MAGNI PAOLO ,  POGGESI ITALO ,  ROCCHETTI MAURIZIO

发明人： BELLAZZI RICCARDO ,  DE NICOLAO GIUSEPPE ,  MAGNI PAOLO ,  POGGESI ITALO ,  ROCCHETTI MAURIZIO

IPC分类号： G01N33/15 ,  G05B17/02 ,  G06F17/18 ,  G06F19/00

CPC分类号： G06F19/3456 ,  G05B17/02 ,  G06F19/325 ,  G16H10/20 ,  G16H10/60 ,  G16H50/50

摘要： A method of estimating the average exposure within a population of subjects to a pharmacological substance, administered according to a given protocol, by estimating the area under the concentration curve (AUC), characterised in that the area under the population concentration curve is estimated by the steps of obtaining measurements of the drug concentrations in each of the subjects at any time during the study, independently from the time when measurements of the drug concentration level in the other subjects are being taken; building a hierarchical stochastic model composed of the population and of the individual levels; determining the posterior probability distribution of the average AUC from the sample data and hence the average population AUC. The exposure of an individual and its precision within the sample of individuals can be determined by determining the posterior probability distribution of the individual AUC from the sample data. The posterior probability model may be obtained by using a Markov Chain Monte Carlo algorithm, such as Gibbs Sampling.

摘要翻译： 根据给定方案，通过估计浓度曲线下面积（AUC），估算受试者群体中药物物质平均暴露量的方法，其特征在于，根据群体浓度曲线下的面积由 在研究期间的任何时间获得每个受试者的药物浓度的测量的步骤，独立于其他受试者的药物浓度水平的测量时间; 建立由人口和个人层次组成的分层随机模型; 从样本数据确定平均AUC的后验概率分布，从而确定平均群体AUC。 可以通过从样本数据确定个体AUC的后验概率分布来确定个体的暴露及其在个体样本内的精确度。 后验概率模型可以通过使用马尔科夫链蒙特卡罗算法（例如Gibbs Sampling）获得。

公开(公告)号：WO2003079004A2

公开(公告)日：2003-09-25

申请号：PCT/EP2003/002689

申请日：2003-03-14

申请人： PHARMACIA ITALIA S.P.A. ,  UNIVERSITA' DEGLI STUDI DI PAVIA ,  CAMMIA, Cristiano ,  DE NICOLAO, Giuseppe ,  POGGESI, Italo ,  ROCCHETTI, Maurizio

发明人： CAMMIA, Cristiano ,  DE NICOLAO, Giuseppe ,  POGGESI, Italo ,  ROCCHETTI, Maurizio

IPC分类号： G01N33/00

CPC分类号： G06F19/3456 ,  G06F19/00 ,  G06F19/321 ,  G16H50/50

摘要： The present invention relates to a method for estimating or predicting the anti-tumor activity of a compound and for estimating or predicting the tumor growth in mammals; the estimation of the anti-tumor activity of a compound administered to mammals developing a tumor comprises a) measuring the tumor weight in time; b) measuring the concentration of the compound in time; c) calculating, on the basis of said measures, the following kinetic parameters of the tumor growth: a parameter (L 0 ), representative of the portion of the tumor cells present at the instant t 0 =0 that succeeds in taking root and in starting the tumor cells proliferation in the mammals; an index (λ O ) of the production rate of the tumor cells during an exponential phase of the tumor growth; -an index (λ 1 ) of the tumor cells mass produced in the time unit during a linear phase of the tumor growth; and the following pharmacodynamic parameters of the compound: an index (K 1 ) of the tumor cells death rate; an index (K 2 ) of the potency of the compound; and d) calculating, on the basis of said kinetic and pharmacodynamic parameters, tumor growth curves. The invention, applicable in the pharmaceutical field, allows to make the best use of all the information generated during the preclinical studies and results to be sufficiently simple also allowing to get good estimates or predictions regardless of the uncertainties on the mode of action. The invention further allows to employ a small number of parameters, therefore avoiding time consumption as well as a number of mechanistic observations.

摘要翻译： 本发明涉及一种用于估计或预测化合物的抗肿瘤活性并估计或预测哺乳动物肿瘤生长的方法; 估计施用于发展肿瘤的哺乳动物的化合物的抗肿瘤活性包括：a）及时测量肿瘤重量; b）及时测定化合物的浓度; c）根据所述措施，计算肿瘤生长的以下动力学参数：代表在成功获得根的时刻t0 = 0处存在的肿瘤细胞部分的参数（L0），并开始 哺乳动物肿瘤细胞增殖; 肿瘤生长指数期肿瘤细胞产生率的指标（lambdO）; - 在肿瘤生长的线性期间以时间单位产生的肿瘤细胞量的指数（lambd1）; 和化合物的以下药效学参数：肿瘤细胞死亡率的指标（K1）; 该化合物的效力指数（K2）; 和d）根据所述动力学和药效学参数计算肿瘤生长曲线。 适用于制药领域的本发明允许最好地利用在临床前研究期间产生的所有信息，并且结果足够简单，还允许获得良好的估计或预测，而不考虑作用模式的不确定性。 本发明还允许采用少量参数，因此避免了时间消耗以及许多机械观察。