Method and system for obtaining and using pharmacokinetic data in drug administration
Inventors
Assignees
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Publication Number
US-11062797-B2
Publication Date
2021-07-13
Expiration Date
Abstract
There is provided a method for dosing a drug to a patient, including (a) administering the drug to the patient according to a titration dosing schedule, where the titration dosing schedule is determined from a database storing data containing observations of previous patient responses to the drug, and the titration dosing schedule is associated with a subcohort of a cohort of patients, where a subcohort classification is based on one or more factors associated with variability of the drug; (b) monitoring the patient during the administering (a) to determine when a desired clinical endpoint is reached; (c) administering the drug to the patient according to a maintenance dosing schedule, where the maintenance dosing schedule is based on an estimate of drug level, where the estimate is based on (i) when the desired clinical endpoint is reached, and (ii) a pharmacokinetic model for the subcohort; and (d) updating the database to incorporate data from the monitoring (b) of the patient.
Core Innovation
The described invention provides a method and system for dosing a drug to a patient using a titration dosing schedule obtained from a database and specific to a subcohort of a cohort of patients. The patient is assigned to the subcohort based at least on a match between race or ethnicity of the patient and the patients of the subcohort, and the schedule is based on observations of previous patient responses to the drug.
The titration dosing includes administering the drug as a bolus and subsequently at an initial infusion rate that is constant. During the first administering, the patient is monitored to determine when a desired clinical endpoint is reached, where the desired clinical endpoint is sedation, visible airway collapse, airway obstruction, or loss of genioglossus tone (or loss genioglossus tissue).
Once the desired clinical endpoint is reached, the invention determines an effect-site concentration by estimating a drug level according to hybrid pharmacokinetic/pharmacodynamic modeling based on an amount of administered drug when the desired clinical endpoint was reached and a pharmacokinetic model for the subcohort. A maintenance dosing schedule is then formulated at a secondary infusion rate that is constant to maintain the determined effect-site concentration.
The method performs a second administering responsive to determining the desired clinical endpoint is reached, where the second administering is performed according to the maintenance dosing schedule. Patient data are collected during the second administering and used to update the subcohort to include the collected patient data, and the pharmacokinetic model is updated by minimizing a difference between a probability density function for the updated subcohort and the cohort. The titration dosing schedule is also updated to incorporate data from the monitoring, and the hybrid pharmacokinetic/pharmacodynamic modeling is performed without a physical connection to the pump or other drug delivery device associated with the first and second administrations.
Claims Coverage
The independent claims cover a drug-dosing method, a drug-dosing system, a nontransitory computer-readable storage medium, and an additional method for determining dosing for a new patient. Across the independent claims, the inventive features center on subcohort-specific dosing, endpoint-based effect-site concentration determination, constant-rate bolus and infusion dosing phases, and iterative database and model updates using probability density function minimization, with hybrid modeling performed without a physical connection to the drug delivery pump or device.
Database-derived titration schedule specific to a subcohort
A titration dosing schedule obtained from a database is specific to a subcohort of a cohort of patients and is based on observations of previous patient responses to the drug.
Subcohort assignment based on race or ethnicity
The patient is assigned to the subcohort based at least on a match between one of race or ethnicity of the patient and the patients of the subcohort.
Bolus followed by constant initial infusion rate during first administering
The first administration includes administering the drug as a bolus and, subsequently, at an initial infusion rate that is constant.
Monitoring to determine when a desired clinical endpoint is reached
The patient is monitored during the first administration to determine when a desired clinical endpoint is reached, wherein the desired clinical endpoint is sedation, visible airway collapse, airway obstruction, or loss of genioglossus tone (or loss of genioglossus tissue).
Effect-site concentration estimation using hybrid pharmacokinetic/pharmacodynamic modeling for the subcohort
An effect-site concentration is determined once the desired clinical endpoint is reached by estimating a drug level determined according to hybrid pharmacokinetic/pharmacodynamic modeling based on an amount of administered drug when the desired clinical endpoint was reached and a pharmacokinetic model for the subcohort.
Maintenance dosing schedule at a constant secondary infusion rate
A maintenance dosing schedule is formulated at a secondary infusion rate to maintain the determined effect-site concentration, wherein the secondary infusion rate is constant.
Second administering according to the maintenance dosing schedule
A second administering is performed responsive to determining that the desired clinical endpoint is reached, wherein the second administering is performed according to the maintenance dosing schedule.
Collecting patient data and updating the subcohort
Patient data are collected during the second administering and the subcohort is updated to include the collected patient data.
Updating pharmacokinetic model by minimizing probability density function difference
The pharmacokinetic model for the subcohort is updated using the collected patient data by minimizing a difference between a probability density function for the updated subcohort and the cohort.
Updating the titration dosing schedule using monitoring data
The titration dosing schedule is updated to incorporate data from the monitoring of the patient, including calculating an update to the titration schedule for a new patient.
Hybrid pharmacokinetic/pharmacodynamic modeling without a physical connection to the pump or device
The hybrid pharmacokinetic/pharmacodynamic modeling is performed without a physical connection to the pump or other drug delivery device associated with the first administering and the second administering.
System processing circuitry configured to perform the dosing workflow
Processing circuitry is configured to perform the database-derived subcohort-specific titration dosing workflow including first administration with a bolus and constant initial infusion rate, monitoring to endpoint, effect-site concentration estimation using hybrid pharmacokinetic/pharmacodynamic modeling, and second administration according to a constant-rate maintenance schedule, along with subcohort, model, and schedule updates.
Computer-readable instructions to perform the dosing method
Computer executable instructions stored on a nontransitory computer-readable storage medium, when executed, cause a processor to perform the dosing method including database-derived subcohort titration, endpoint monitoring, hybrid modeling effect-site estimation, maintenance scheduling, patient data collection, and model and schedule updating, with hybrid modeling without a physical connection to the pump or device.
The claim set covers dosing workflows that use a database-derived subcohort-specific titration schedule, assign patients to subcohorts using demographic matching, monitor for a desired clinical endpoint, estimate effect-site concentration using hybrid pharmacokinetic/pharmacodynamic modeling for the subcohort, then administer a second phase using a constant-rate maintenance dosing schedule. The workflow is iteratively updated using collected monitoring and observation data to update the subcohort and a pharmacokinetic model via minimizing differences between probability density functions, and to update the titration dosing schedule, with hybrid modeling performed without a physical connection to the pump or other drug delivery device.
Stated Advantages
Documented Applications
Drug dosing for patients for sedation and visible airway collapse, airway obstruction, or loss of genioglossus tone (loss of genioglossus tissue) as a desired clinical endpoint during monitoring.
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