Novel methods for medicinal dosage determination and diagnosis

Abstract

The present invention is directed to systems and methods for diagnosing tissue abnormality or diseases, determining effective drug dosages, and monitoring therapeutic drug treatments. The methods and systems described utilize tissue imaging in situ and computer modeling.

1 . A method for determining quantitative pharmacodynamic parameters for a pharmacologically active agent in a biological organism, the method comprising:
 a) administering to a biological organism a single dose of the pharmacologically active agent;   b) collecting biological imaging data comprising the biological organism's response to the single dose of the pharmacologically active agent administered in a), wherein, the collection of biological imaging data comprises the response of the biological organism which has not reached a steady state; and   c) fitting predetermined pharmacokinetic-pharmacodynamic models to said imaging data to determine the quantitative pharmacodynamic parameters for said pharmacologically active agent comprising:
 i) setting up fit parameters and choosing a fit method; 
 ii) computing best-fit parameters and their goodness of fit to the biological data using the selected fit method; 
 iii) computing the statistical significance of the best-fit parameters; and 
 iv) generating an output. 
   
     
     
         2 . The method of  claim 1 , wherein the imaging data is collected on a magnetic resonance imaging device. 
     
     
         3 . The method of  claim 1 , wherein the imaging data is collected on a magnetic resonance imaging device sensitive to a blood oxygen level dependent signal. 
     
     
         4 . The method of  claim 1 , wherein the imaging data is collected using Positron Emission Tomography. 
     
     
         5 . The method of  claim 1 , wherein the imaging data is collected on a Single Photon Emission Computed Tomography imaging device. 
     
     
         6 . The method of  claim 1 , wherein the pharmacologically active agent is a medicament and the organism is a human. 
     
     
         7 . The method of  claim 1 , wherein the quantitative pharmacodynamic parameters are selected from the group consisting of E max , Hill coefficient, EC 50 , ED 50 , k e0 , and t 1/2  eq. 
     
     
         8 . The method of  claim 1 , wherein the imaging method does not provide quantitative measures. 
     
     
         9 . The method of  claim 8  wherein the nonquantitative measurements are used without modification in fitting predetermined pharmacokinetic-pharmacodynamic models. 
     
     
         10 . A method for determining quantitative pharmacodynamic parameters for a pharmacologically active agent in a biological organism, the method comprising:
 a) administering to a biological organism a single dose of the pharmacologically active agent;   b) collecting biological imaging data comprising the biological organism's response to the single dose of the pharmacologically active agent administered in a), in a single imaging session; wherein, the single imaging session begins before the administration of the single dose and is completed after the administration of the single dose; and   c) fitting predetermined pharmacokinetic-pharmacodynamic models to said imaging data to determine the quantitative pharmacodynamic parameters for said pharmacologically active agent comprising:
 i) setting up fit parameters and choosing a fit method; 
 ii) computing best-fit parameters and their goodness of fit to the biological data using the selected fit method; 
 iii) computing the statistical significance of the best-fit parameters; and 
 iv) generating an output. 
   
     
     
         11 . The method of  claim 10 , wherein the imaging data is collected on a magnetic resonance imaging device. 
     
     
         12 . The method of  claim 10 , wherein the imaging data is collected on a magnetic resonance imaging device sensitive to blood oxygen level dependent signal. 
     
     
         13 . The method of  claim 10 , wherein the imaging data is collected using Positron Emission Tomography. 
     
     
         14 . The method of  claim 10 , wherein the imaging data is collected on a Single Photon Emission Computed Tomography imaging device. 
     
     
         15 . The method of  claim 10 , wherein the pharmacologically active agent is a medicament and the organism is a human. 
     
     
         16 . The method of  claim 10 , wherein the quantitative pharmacodynamic parameters are selected from the group consisting of E max , Hill coefficient, EC 50 , ED 50 , k e0 , and t 1/2  eq. 
     
     
         17 . The method of  claim 10 , wherein the imaging method does not provide quantitative measures. 
     
     
         18 . The method of  claim 17 , wherein the nonquantitative measurements are used without modification in fitting predetermined pharmacokinetic-pharmacodynamic models. 
     
     
         19 . A method for quantitatively characterizing an organ's response to a pharmaceutically active agent, comprising:
 a) administering to a biological organism a plurality of doses, of a pharmacologically active agent, over a sufficiently brief time interval, wherein the response of the biological organism to the pharmacologically active agent does not return to baseline between doses;   b) collecting nonquantitative biological imaging data comprising a response of the organ to the plurality of doses of the pharmacologically active agent administered in a), in a single imaging session, over a the sufficiently brief time interval and;   c) determining quantitative pharmacodynamics parameters for the pharmacologically active agent by fitting predetermined pharmacokinetic-pharmacodynamic models to the nonquantitative biological imaging data comprising:
 i) setting up fit parameters and choosing a fit method; 
 ii) computing best-fit parameters and their goodness of fit to the biological data using the selected fit method; 
 iii) computing the statistical significance of the best-fit parameters; and 
 iv) generating an output.