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Patent · US11081211B2 · B2 · US

Method and apparatus for providing a pharmacokinetic drug dosing regimen

(11) Publication number
US11081211B2
(21) Application number
17/070,599
(22) Filing date
2020-10-14
(30) Priority date
2013-06-20
(43) Publication date
2021-08-03
(45) Date of grant
2021-08-03
(51) IPC
G06N 7/00; G16C 20/50; G16C 20/70; G16C 20/30; G16H 20/17; G16H 50/20; G16H 50/70
(52) CPC
  • G16C Computational chemistry; chemoinformatics; computational materials science: 20/30, 20/50, 20/70
  • A61K Preparations for medical, dental or toiletry purposes: 49/0004
  • A61P Specific therapeutic activity of chemical compounds or medicinal preparations: 7/04
  • G06N Computing arrangements based on specific computational models: 7/00, 7/005, 7/01
  • G16H Healthcare informatics, i.e. information and communication technology [ICT] specially adapted for the handling or processing of medical or healthcare data: 20/10, 20/17, 50/20, 50/50, 50/70
(73) Assignee
Baxalta GmbH; Baxalta Inc
(72) Inventors
Kameswara Rao Kuchimanchi; Alexandra Loew-Baselli; Gerald Spotts; MyungShin Oh; Michael Don Hale; Martin Wolfsegger
(54) Title
Method and apparatus for providing a pharmacokinetic drug dosing regimen
(57) Abstract

Systems and methods providing a clotting factor VIII dosing regimen are disclosed. The systems and methods include determining an estimated pharmacokinetic profile of a patient using a Bayesian model of pharmacokinetic profiles of sampled patients. The systems and methods can determine a first dosing regimen for a first dosing interval including (i) a first dosage and (ii) a first therapeutic plasma protein level in the patient varying over time based at least upon the estimated pharmacokinetic profile. The systems and methods can determine a second dosing regimen for a second dosing interval including (i) a second dosage and (ii) a second therapeutic plasma protein level in the patient varying over time. The estimated pharmacokinetic profile can be adjusted based on previous patient treatments. Further, a user can select which days a dosage is to be applied such that the protein level does not fall below a target trough.

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Claims (9)

  1. An apparatus comprising: a processor; a non-transitory storage medium comprising memory storing instructions that are configured, when executed by the processor, to cause the apparatus to perform a procedure comprising: determining, via the processor, an estimated pharmacokinetic profile of a patient using a Bayesian model of pharmacokinetic profiles of sampled patients, the estimated pharmacokinetic profile based upon at least one of a body weight or an age of the patient; determining, via the processor, a first dosing regimen for a first specified dosing interval including (i) a first dosage and (ii) a first therapeutic plasma protein level in the patient varying over time based at least upon the estimated pharmacokinetic profile; determining, via the processor, a second dosing regimen for a second specified dosing interval including (i) a second dosage and (ii) a second therapeutic plasma protein level in the patient varying over time based at least upon the estimated pharmacokinetic profile and in response to receiving a change to at least one of a minimum therapeutic plasma protein level, dosage interval, or dosage of the therapeutic plasma protein, wherein the change to the at least one of the minimum therapeutic plasma protein level, the dosage interval, or the dosage is received via a graphical user interface (GUI) associated with the apparatus that includes fields for user input for adjusting at least one of the minimum therapeutic plasma protein level, the dosage interval, or the dosage; displaying the second dosing regimen on a client device and within the GUI; adjusting, via the processor, the estimated pharmacokinetic profile of the patient upon previous treatments of the patient; and determining, via the processor, if the patient has a therapeutic plasma protein half-life greater than a predetermined threshold, wherein: a first weighting factor is applied to the Bayesian model of pharmacokinetic profiles of sampled patients if the half-life of the patient is greater than the predetermined threshold, and a second weighting factor, less than the first weighting factor, is applied to the Bayesian model of pharmacokinetic profiles of sampled patients if the half-life of the patient is less than the predetermined threshold.
  2. The apparatus of claim 1, wherein the second specified dosing interval is longer than the first specified dosing interval.
  3. The apparatus of claim 2, wherein the first specified dosing interval is 48 hours and the second specified dosing interval is 72 hours.
  4. The apparatus of claim 1, wherein the first dosage is determined such that the first therapeutic plasma protein level in the patient does not fall below an initial minimum concentration threshold, and wherein the initial minimum concentration threshold is less than 20% relative to baseline plasma protein level for the patient.
  5. The apparatus of claim 1, wherein the first therapeutic plasma protein level in the patient is based upon at least one of an initial minimum concentration threshold, the first dosage, or the first specified dosing interval, and the second therapeutic plasma protein level in the patient is based upon at least one of the initial minimum concentration threshold, the first dosage, or the first specified dosing interval.
  6. The apparatus of claim 1, wherein the Bayesian model includes a two-compartment model having a first compartment corresponding to a time to metabolize the therapeutic plasma protein and a second compartment corresponding to a dose for achieving a certain amount of the therapeutic plasma protein within the patient.
  7. The apparatus of claim 1, wherein the minimum therapeutic plasma protein level is a first minimum protein level, and wherein the instructions, when executed by the processor, cause the apparatus to perform the procedure comprising: receiving, at the processor, a selection of a second minimum protein level greater that the first minimum protein level; determining, via the processor, a duration of time the second therapeutic plasma protein level in the patient is below the second minimum protein level; and displaying, in the GUI, a graphical representation of the duration of time in conjunction with the display of the second dosing regimen.
  8. The apparatus of claim 7, wherein the duration of time is further based on the time the second therapeutic plasma protein level is above the first minimum protein level.
  9. The apparatus of claim 1, wherein the estimated pharmacokinetic profile is based at least on two blood samples collected from the patient after an infusion of therapeutic plasma protein.

Description

Clotting factor VIII is a blood-clotting protein that is activated in response to an injury or bleed. Individuals with relatively low levels of clotting factor VIII are susceptible to internal or external episodes of prolonged bleeding resulting from an injury and/or spontaneous bleeding without a cause. While skin bleeds are not serious, internal bleeding of joints, muscles, and organs can cause permanent damage, disfigurement, or even death.

Patients with hemophilia A have a genetic deficiency that causes low levels of clotting factor VIII. The amount of clotting factor VIII in a patient is expressed as a percentage relative to a normal level. Patients with 5 to 40% of clotting factor VIII are considered to have a mild form of hemophilia A while patients with 1 to 5% of clotting factor VIII are considered to have a moderate form of hemophilia A. Patients with less than 1% of clotting factor VIII are considered to have a severe form of hemophilia A.

Treatment of patients with hemophilia A (or patients that otherwise have low levels of clotting factor VIII) includes providing these patients with periodic infusions of a clotting factor concentrate (e.g., therapeutic plasma protein). The clotting factor concentrate acts as a replacement or supplement for the patient's natural occurring clotting factor VIII. One example of such a therapeutic plasma protein is Shire's ADVATE drug. In some instances, patients receive the therapeutic plasma protein in response to having an uncontrolled internal bleed.

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Record as JSON 
{
  "publication_number": "US11081211B2",
  "country": "US",
  "kind": "B2",
  "title": "Method and apparatus for providing a pharmacokinetic drug dosing regimen",
  "abstract": "Systems and methods providing a clotting factor VIII dosing regimen are disclosed. The systems and methods include determining an estimated pharmacokinetic profile of a patient using a Bayesian model of pharmacokinetic profiles of sampled patients. The systems and methods can determine a first dosing regimen for a first dosing interval including (i) a first dosage and (ii) a first therapeutic plasma protein level in the patient varying over time based at least upon the estimated pharmacokinetic profile. The systems and methods can determine a second dosing regimen for a second dosing interval including (i) a second dosage and (ii) a second therapeutic plasma protein level in the patient varying over time. The estimated pharmacokinetic profile can be adjusted based on previous patient treatments. Further, a user can select which days a dosage is to be applied such that the protein level does not fall below a target trough.",
  "claims": [
    "1. An apparatus comprising: a processor; a non-transitory storage medium comprising memory storing instructions that are configured, when executed by the processor, to cause the apparatus to perform a procedure comprising: determining, via the processor, an estimated pharmacokinetic profile of a patient using a Bayesian model of pharmacokinetic profiles of sampled patients, the estimated pharmacokinetic profile based upon at least one of a body weight or an age of the patient; determining, via the processor, a first dosing regimen for a first specified dosing interval including (i) a first dosage and (ii) a first therapeutic plasma protein level in the patient varying over time based at least upon the estimated pharmacokinetic profile; determining, via the processor, a second dosing regimen for a second specified dosing interval including (i) a second dosage and (ii) a second therapeutic plasma protein level in the patient varying over time based at least upon the estimated pharmacokinetic profile and in response to receiving a change to at least one of a minimum therapeutic plasma protein level, dosage interval, or dosage of the therapeutic plasma protein, wherein the change to the at least one of the minimum therapeutic plasma protein level, the dosage interval, or the dosage is received via a graphical user interface (GUI) associated with the apparatus that includes fields for user input for adjusting at least one of the minimum therapeutic plasma protein level, the dosage interval, or the dosage; displaying the second dosing regimen on a client device and within the GUI; adjusting, via the processor, the estimated pharmacokinetic profile of the patient upon previous treatments of the patient; and determining, via the processor, if the patient has a therapeutic plasma protein half-life greater than a predetermined threshold, wherein: a first weighting factor is applied to the Bayesian model of pharmacokinetic profiles of sampled patients if the half-life of the patient is greater than the predetermined threshold, and a second weighting factor, less than the first weighting factor, is applied to the Bayesian model of pharmacokinetic profiles of sampled patients if the half-life of the patient is less than the predetermined threshold.",
    "2. The apparatus of claim 1, wherein the second specified dosing interval is longer than the first specified dosing interval.",
    "3. The apparatus of claim 2, wherein the first specified dosing interval is 48 hours and the second specified dosing interval is 72 hours.",
    "4. The apparatus of claim 1, wherein the first dosage is determined such that the first therapeutic plasma protein level in the patient does not fall below an initial minimum concentration threshold, and wherein the initial minimum concentration threshold is less than 20% relative to baseline plasma protein level for the patient.",
    "5. The apparatus of claim 1, wherein the first therapeutic plasma protein level in the patient is based upon at least one of an initial minimum concentration threshold, the first dosage, or the first specified dosing interval, and the second therapeutic plasma protein level in the patient is based upon at least one of the initial minimum concentration threshold, the first dosage, or the first specified dosing interval.",
    "6. The apparatus of claim 1, wherein the Bayesian model includes a two-compartment model having a first compartment corresponding to a time to metabolize the therapeutic plasma protein and a second compartment corresponding to a dose for achieving a certain amount of the therapeutic plasma protein within the patient.",
    "7. The apparatus of claim 1, wherein the minimum therapeutic plasma protein level is a first minimum protein level, and wherein the instructions, when executed by the processor, cause the apparatus to perform the procedure comprising: receiving, at the processor, a selection of a second minimum protein level greater that the first minimum protein level; determining, via the processor, a duration of time the second therapeutic plasma protein level in the patient is below the second minimum protein level; and displaying, in the GUI, a graphical representation of the duration of time in conjunction with the display of the second dosing regimen.",
    "8. The apparatus of claim 7, wherein the duration of time is further based on the time the second therapeutic plasma protein level is above the first minimum protein level.",
    "9. The apparatus of claim 1, wherein the estimated pharmacokinetic profile is based at least on two blood samples collected from the patient after an infusion of therapeutic plasma protein."
  ],
  "description_excerpt": "Clotting factor VIII is a blood-clotting protein that is activated in response to an injury or bleed. Individuals with relatively low levels of clotting factor VIII are susceptible to internal or external episodes of prolonged bleeding resulting from an injury and/or spontaneous bleeding without a cause. While skin bleeds are not serious, internal bleeding of joints, muscles, and organs can cause permanent damage, disfigurement, or even death.\n\nPatients with hemophilia A have a genetic deficiency that causes low levels of clotting factor VIII. The amount of clotting factor VIII in a patient is expressed as a percentage relative to a normal level. Patients with 5 to 40% of clotting factor VIII are considered to have a mild form of hemophilia A while patients with 1 to 5% of clotting factor VIII are considered to have a moderate form of hemophilia A. Patients with less than 1% of clotting factor VIII are considered to have a severe form of hemophilia A.\n\nTreatment of patients with hemophilia A (or patients that otherwise have low levels of clotting factor VIII) includes providing these patients with periodic infusions of a clotting factor concentrate (e.g., therapeutic plasma protein). The clotting factor concentrate acts as a replacement or supplement for the patient's natural occurring clotting factor VIII. One example of such a therapeutic plasma protein is Shire's ADVATE drug. In some instances, patients receive the therapeutic plasma protein in response to having an uncontrolled internal bleed.",
  "cpc": [
    "G16C 20/30",
    "A61K 49/0004",
    "A61P 7/04",
    "G06N 7/00",
    "G06N 7/005",
    "G06N 7/01",
    "G16C 20/50",
    "G16C 20/70",
    "G16H 20/10",
    "G16H 20/17",
    "G16H 50/20",
    "G16H 50/50",
    "G16H 50/70"
  ],
  "ipc": [
    "G06N 7/00",
    "G16C 20/50",
    "G16C 20/70",
    "G16C 20/30",
    "G16H 20/17",
    "G16H 50/20",
    "G16H 50/70"
  ],
  "assignees": [
    "Baxalta GmbH",
    "Baxalta Inc"
  ],
  "inventors": [
    "Kameswara Rao Kuchimanchi",
    "Alexandra Loew-Baselli",
    "Gerald Spotts",
    "MyungShin Oh",
    "Michael Don Hale",
    "Martin Wolfsegger"
  ],
  "filing_date": "2020-10-14",
  "publication_date": "2021-08-03",
  "grant_date": "2021-08-03",
  "priority_date": "2013-06-20",
  "application_number": "US-202017070599-A",
  "family_id": "60041975",
  "cited_by_count": 9,
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}

Record 1,546 of 8,000 in Patents full text (MLC-0201). Request the full dataset.