Multiple compartment dosing model
First Claim
1. A method for modeling a dosing regimen for a medicament, the method comprising:
- providing a system including at least two biocompartments selected from the group consisting of intracellular and extracellular regions;
determining, by a processing device, steady state levels in each of said at least two biocompartments by assigning variables to represent a protein production rate of at least one protein in one of said at least two biocompartments, a degradation rate constant of said at least one protein for each of said at least two biocompartments, and a transport rate constant of said at least one protein between said at least two biocompartments using a set of equations;
modifying, by the processing device, values of said assigned variables in said set of equations to use said set of equations to calculate an amount of said at least one protein in one of said at least two biocompartments to which said at least one protein is being transported, as a function of time, said set of equations reflecting selected characteristics of said at least one protein and one or more drug pulse parameters, said one or more drug pulse parameters include a start time, a duration, an interval time, a number of pulses, an amount of drug, and a number of times settings are repeated;
calculating, by the processing device, a weighted value of said at least one protein in said one of said at least two biocompartments to which said at least one protein is being transported, wherein said weighted value is a result of multiplying a calculated factor by an amount of said at least one protein in said one of said at least two biocompartments to which said at least one protein is being transported, said calculated factor being determined using a drug concentration pulse curve and a set of input parameters including a substrate concentration, a maximum drug concentration, a rise time, and a drug elimination half-life, said drug concentration pulse curve and said set of input parameters associated with a drug;
integrating, by the processing device, said weighted value over a time period to determine a weighted area-under a curve associated with said integrating said weighted value;
calculating, by the processing device, a non-drug value of said at least one protein in said one of said at two biocompartments to which said at least one protein is being transported, wherein said non-drug value is an amount of said at least one protein in said one of said at least two biocompartments to which said at least one protein is being transported without addition of said drug;
integrating, by the processing device, said non-drug value over said time period to find a non-drug area under a curve associated with said integrating of said non-drug value; and
evaluating, by the processing device, one or more dosing regimens by comparing said weighted area and said non-drug area of said at least one protein in said one of said at least two biocompartments to which said at least one protein is being transported over said time period to determine a net effect of said drug over said time period.
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Abstract
The method for modeling a dosing regimen for a medicament includes providing a system having at least two biocompartments. The method determines steady state levels in each of the biocompartments. After that, the method provides for modifying values to calculate an amount of at least one protein in one of the biocompartments to which the protein is being transported. Next, the method calculates and integrates a weighted value of the protein to find a weighted area under the curve. Then, the method calculates and integrates a non-drug value of the protein to find a non-drug area under the curve. Finally, the method evaluates one or more dosing regimens by comparing the weighted area under the curve and the non-drug area under the curve of the protein to determine a net effect of the drug over the time period.
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Citations
20 Claims
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1. A method for modeling a dosing regimen for a medicament, the method comprising:
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providing a system including at least two biocompartments selected from the group consisting of intracellular and extracellular regions; determining, by a processing device, steady state levels in each of said at least two biocompartments by assigning variables to represent a protein production rate of at least one protein in one of said at least two biocompartments, a degradation rate constant of said at least one protein for each of said at least two biocompartments, and a transport rate constant of said at least one protein between said at least two biocompartments using a set of equations; modifying, by the processing device, values of said assigned variables in said set of equations to use said set of equations to calculate an amount of said at least one protein in one of said at least two biocompartments to which said at least one protein is being transported, as a function of time, said set of equations reflecting selected characteristics of said at least one protein and one or more drug pulse parameters, said one or more drug pulse parameters include a start time, a duration, an interval time, a number of pulses, an amount of drug, and a number of times settings are repeated; calculating, by the processing device, a weighted value of said at least one protein in said one of said at least two biocompartments to which said at least one protein is being transported, wherein said weighted value is a result of multiplying a calculated factor by an amount of said at least one protein in said one of said at least two biocompartments to which said at least one protein is being transported, said calculated factor being determined using a drug concentration pulse curve and a set of input parameters including a substrate concentration, a maximum drug concentration, a rise time, and a drug elimination half-life, said drug concentration pulse curve and said set of input parameters associated with a drug; integrating, by the processing device, said weighted value over a time period to determine a weighted area-under a curve associated with said integrating said weighted value; calculating, by the processing device, a non-drug value of said at least one protein in said one of said at two biocompartments to which said at least one protein is being transported, wherein said non-drug value is an amount of said at least one protein in said one of said at least two biocompartments to which said at least one protein is being transported without addition of said drug; integrating, by the processing device, said non-drug value over said time period to find a non-drug area under a curve associated with said integrating of said non-drug value; and evaluating, by the processing device, one or more dosing regimens by comparing said weighted area and said non-drug area of said at least one protein in said one of said at least two biocompartments to which said at least one protein is being transported over said time period to determine a net effect of said drug over said time period. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9)
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10. A system for modeling a dosing regimen of a medicament, the system comprising:
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a display device; a data store comprising a plurality of values for modeling a dosing regime of a medicament; and a service delivery device operatively connected to said display device and said data store, said service delivery device including a processor and a memory for storing instructions that, in response to receiving a request to model the dosing regimen of a medicament, causes the processor to; provide a system including at least two biocompartments selected from the group consisting of intracellular and extracellular regions; determine steady state levels in each of said at least two biocompartments by assigning variables to represent a protein production rate of at least one protein in one of said at least two biocompartments, a degradation rate constant of said at least one protein for each of said at least two biocompartments, and a transport rate constant of said at least one protein between said at least two biocompartments using a set of equations; modify values of said assigned variables in said set of equations to use said set of equations to calculate an amount of said at least one protein in one of said at least two biocompartments to which said at least one protein is being transported, as a function of time, said set of equations reflecting selected characteristics of said at least one protein and one or more drug pulse parameters, said one or more drug pulse parameters include a start time, a duration, an interval time, a number of pulses, an amount of drug, and a number of times settings are repeated; calculate a weighted value of said at least one protein in said one of said at least two biocompartments to which said at least one protein is being transported, wherein said weighted value is a result of multiplying a calculated factor by an amount of said at least one protein in said one of said at least two biocompartments to which said at least one protein is being transported, said calculated factor being determined using a drug concentration pulse curve and a set of input parameters including a substrate concentration, a maximum drug concentration, a rise time, and a drug elimination half-life, said drug concentration pulse curve and a set of input parameters associated with a drug; integrate said weighted value over a time period to determine a weighted area under a curve associated with integration of said weighed value; calculate a non-drug value of said at least one protein in said one of said at two biocompartments to which said at least one protein is being transported, wherein said non-drug value is an amount of said at least one protein in said one of said at least two biocompartments to which said at least one protein is being transported without addition of said drug; integrate said non-drug value over said time period to find a non-drug area under a curve associated with integration of said non-drug value; and evaluate one or more dosing regimens by comparing said weighted area and said non-drug area of said at least one protein in said one of said at least two biocompartments to which said at least one protein is being transported over said time period to determine a net effect of said drug over said time period. - View Dependent Claims (11, 12, 13, 14, 15, 16, 17, 18, 19)
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20. A non-transitory computer-readable medium for modeling a dosing regimen for a medicament comprising instructions executable by a computing device that, when applied to the computing device causes the computing device to:
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provide a system including at least two biocompartments selected from the group consisting of intracellular and extracellular regions; determine steady state levels in each of said at least two biocompartments by assigning variables to represent a protein production rate of at least one protein in one of said at least two biocompartments, a degradation rate constant of said at least one protein for each of said at least two biocompartments, and a transport rate constant of said at least one protein between said at least two biocompartments using a set of equations; modify values of said assigned variables in said set of equations to use said set of equations to calculate an amount of at least one protein in one of said at least two biocompartments to which said at least one protein is being transported, as a function of time, said set of equations reflecting selected characteristics of said at least one protein and one or more drug pulse parameters, said one or more drug pulse parameters include a start time, a duration, an interval time, a number of pulses, an amount of drug, and a number of times settings are repeated; calculate a weighted value of said at least one protein in said one of said at least two biocompartments to which said at least one protein is being transported, wherein said weighted value is a result of multiplying a calculated factor by an amount of said at least one protein in said one of said at least two biocompartments to which said at least one protein is being transported, said calculated factor being determined using a drug concentration pulse curve and a set of input parameters including a substrate concentration, a maximum drug concentration, a rise time, and a drug elimination half-life, said concentration pulse curve and said set of input parameters associated with a drug; integrate said weighted value over a time period to determine a weighted area under a curve associated with said integration of said weighted value; calculate a non-drug value of said at least one protein in said one of said at two biocompartments to which said at least one protein is being transported, wherein said non-drug value is an amount of said at least one protein in said one of said at least two biocompartments to which said at least one protein is being transported without addition of said drug; integrate said non-drug value over said time period to find a non-drug area under a curve associated with said integration of said non-drug value; and evaluate one or more dosing regimens by comparing said weighted area and said non-drug area of said at least one protein in said one of said at least two biocompartments to which said at least one protein is being transported over said time period to determine a net effect of said drug over said time period.
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Specification