Dose determination program and dose determination device

Patent metadata

Field	Value
Publication number	US-11467170-B2
Application number	US-201816622373-A
Country	US
Kind code	B2
Filing date	Jul 17, 2018
Priority date	Jun 14, 2017
Publication date	Oct 11, 2022
Grant date	Oct 11, 2022

Abstract

A dose determination program for an erythropoiesis-stimulating agent that is executable by a computer. The program causes the computer to perform: obtaining a predetermined target hemoglobin concentration; obtaining a first concentration and a first dose in a stable state in which a hemoglobin concentration is stable at the first concentration by repeatedly administering the first dose a plurality of times, and calculating a second dose of the erythropoiesis-stimulating agent based on the obtained target hemoglobin concentration, the obtained first concentration, and the obtained first dose, the second dose of the erythropoiesis-stimulating agent being to be administered by a fixed amount.

First claim

The invention claimed is:

1. A dose determination device that determines a dose of an erythropoiesis-stimulating agent, the dose determination device comprising:
a computer comprising a CPU, ROM, and RAM, the computer programmed to:
obtain a predetermined target hemoglobin concentration;
obtain a first hemoglobin concentration and a first dose of erythropoiesis-stimulating agent in a stable state in which a hemoglobin concentration is stable at the first hemoglobin concentration when repeatedly administering the first dose a plurality of times over a first time period of three or more months; and
calculate a second constant dose of the erythropoiesis-stimulating agent based on the obtained target hemoglobin concentration, the obtained first hemoglobin concentration, and the obtained first dose, the second constant dose of the erythropoiesis-stimulating agent configured to be administered by a fixed amount,
wherein the computer is programmed to calculate the second constant dose using a predetermined correlation between the second constant dose and each of the first hemoglobin concentration, the first dose, and the target hemoglobin concentration,
wherein the computer is programmed to calculate the correlation based on a first relational expression between the first hemoglobin concentration and the first dose in the stable state and a second relational expression between the target hemoglobin concentration and the second constant dose in a state in which the hemoglobin concentration is stable at the target hemoglobin concentration when repeatedly administering the second constant dose over a second time period of three or more months.

2. The dose determination device according to claim 1 , wherein
in the first relational expression, a logarithmic value of a value obtained by multiplying, by a second coefficient, a value obtained by adding a first coefficient to the first dose, and the first hemoglobin concentration in the stable state are proportional to each other, and
in the second relational expression, a logarithmic value of a value obtained by multiplying, by the second coefficient, a value obtained by adding the first coefficient to the second constant dose, and the target hemoglobin concentration in the state in which the hemoglobin concentration is stable at the target hemoglobin concentration are proportional to each other.

3. The dose determination device according to claim 2 , wherein the first coefficient and the second coefficient differ depending on a case where a patient is in a course of increasing a dose of the erythropoiesis-stimulating agent and a case where the patient is in a course of decreasing the dose of the erythropoiesis-stimulating agent.

4. The dose determination device according to claim 2 , wherein in a case where the erythropoiesis-stimulating agent to be administered is epoetin alfa or epoetin beta, where a unit of a dose of the erythropoiesis-stimulating agent is unit/week and where a patient is in a course of increasing the dose of the erythropoiesis-stimulating agent, when the first coefficient is represented by Ka1, the second coefficient is represented by Kb1, and the first coefficient Ka1 falls within a range of 0≤Ka1≤2700, a value of the second coefficient Kb1 is calculated based on the following formula (1) using the first coefficient Ka1:
Kb 1=(4×10 −17 ×Ka 1 6 )−(4×10 −13 ×Ka 1 5 )+(10 −9 ×Ka 1 4 )−(3×10 −6 ×Ka 1 3 )+(0.0029× Ka 1 2 )−(1.4755× Ka 1)+304.49  Formula (1).

5. The dose determination device according to claim 2 , wherein in a case where the erythropoiesis-stimulating agent to be administered is epoetin alfa or epoetin beta, where a unit of a dose of the erythropoiesis-stimulating agent is unit/week and where a patient is in a course of decreasing the dose of the erythropoiesis-stimulating agent, when the first coefficient is represented by Ka2, the second coefficient is represented by Kb2, and the first coefficient Ka2 falls within a range of 0≤Ka2≤4800, a value of the second coefficient Kb2 is calculated based on the following formula (2) using the first coefficient Ka2:
Kb 2=(−2×10 −17 ×Ka 2 5 )+(4×10 −13 ×Ka 2 4 )−(2×10 −9 ×Ka 2 3 )+(6×10 −6 ×Ka 2 2 )−(0.0086 ×Ka 2)+4.8389  Formula (2).

6. The dose determination device according to claim 2 , wherein in a case where the erythropoiesis-stimulating agent to be administered is darbepoetin alfa, where a unit of a dose of the erythropoiesis-stimulating agent is μg/week and where a patient is in a course of increasing the dose of the erythropoiesis-stimulating agent, when the first coefficient is represented by Ka3, the second coefficient is represented by Kb3, and the first coefficient Ka3 falls within a range of 0≤Ka3≤11, a value of the second coefficient Kb3 is calculated based on the following formula (3) using the first coefficient Ka3:
Kb 3=(0.0564× Ka 3 2 )−(1.0544× Ka 3)+7.2527  Formula (3).

7. The dose determination device according to claim 2 , wherein in a case where the erythropoiesis-stimulating agent to be administered is darbepoetin alfa, where a unit of a dose of the erythropoiesis-stimulating agent is μg/week and where a patient is in a course of decreasing the dose of the erythropoiesis-stimulating agent, when the first coefficient is represented by Ka4, the second coefficient is represented by Kb4, and the first coefficient Ka4 falls within a range of 41≤Ka4≤60, a value of the second coefficient Kb4 is calculated based on the following formula (4) using the first coefficient Ka4:
Kb 4=(−75.67× Ka 4 5 )+(22123× Ka 4 4 )−(3×10 6 ×Ka 4 3 )+(10 8 ×Ka 4 2 )−(4×10 9 ×Ka 4)+5×10 10   Formula (4).

8. The dose determination device according to claim 2 , wherein the second coefficient is represented by a first-degree equation of the first coefficient.

9. The dose determination device according to claim 8 , wherein in a case where the erythropoiesis-stimulating agent to be administered is epoetin alfa or epoetin beta, where a unit of a dose of the erythropoiesis-stimulating agent is unit/week and where a patient is in a course of increasing the dose of the erythropoiesis-stimulating agent, when the first coefficient is represented by Ka1, the second coefficient is represented by Kb1, and the first coefficient Ka1 falls within a range of 600≤Ka1≤1000, a value of the second coefficient Kb1 is calculated based on the following formula (5) using the first coefficient Ka1:
Kb 1=(−0.016× Ka 1)+19.8  Formula (5).

10. The dose determination device according to claim 2 , wherein the second coefficient is represented by a second-degree equation of the first coefficient.

11. The dose determination device according to claim 10 , wherein in a case where the erythropoiesis-stimulating agent to be administered is epoetin alfa or epoetin beta, where a unit of a dose of the erythropoiesis-stimulating agent is unit/week and where a patient is in a course of decreasing the dose of the erythropoiesis-stimulating agent, when the first coefficient is represented by Ka2, the second coefficient is represented by Kb2, and the first coefficient Ka2 falls within a range of 100≤Ka2≤1000, a value of the second coefficient Kb2 is calculated based on the following formula (6) using the first coefficient Ka2:
Kb 2=((0.0002× Ka 2 2 )−(0.6226× Ka 2)+444.25)/100  Formula (6).

12. The dose determination device according to claim 10 , wherein in a case where the erythropoiesis-stimulating agent to be administered is darbepoetin alfa, where a unit of a dose of the erythropoiesis-stimulating agent is μg/week and where a patient is in a course of decreasing the dose of the erythropoiesis-stimulating agent, when the first coefficient is represented by Ka4

Assignees

• Nipro Corp

Inventors

• Shinzato Toru
• Mizuno Wataru
• Saio Hidetoshi

Classifications

• G01N33/48

  Biological material, e.g. blood, urine (G01N33/02, G01N33/26, G01N33/44, G01N33/46 take precedence); Haemocytometers (counting blood corpuscules distributed over a surface by scanning the surface G06M11/02) · CPC title

• A61P7/06

  Antianaemics · CPC title

• A61K38/22

  Hormones (derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin A61K38/33, e.g. corticotropin A61K38/35) · CPC title

• G01N33/726 Primary

  Devices · CPC title

• A61P13/12

  of the kidneys · CPC title