SYSTEMS AND METHODS FOR THERAPY OF KIDNEY DISEASE AND/OR HEART FAILURE USING CHIMERIC NATRIURETIC PEPTIDES

• US 20120220528A1
• Filed: 02/07/2012
• Published: 08/30/2012
• Est. Priority Date: 02/25/2011
• Status: Abandoned Application

• Current Assignee: Capricor Therapeutics, Inc.
• Original Assignee: Medtronic Incorporated (Medtronic Plc)
• Inventors: Van Antwerp, William P., Lieu, Hsiao, Manda, VenKatesh R., Walsh, Andrew J. L., Burnes, John, Evans, Daron
• Application Number:
  US13/368,225
• Publication Number:
  US 20120220528A1
• Time in Patent Office: Days
• US Class Current: 514/12.4
• CPC Class Codes: A61K 38/2242 Atrial natriuretic factor complex: Atriopeptins, atrial natriuretic protein [ANP]; Cardionatrin, Cardiodilatin
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 9/04 Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure

Abstract

Medical systems and methods for treating kidney disease alone, heart failure alone, kidney disease with concomitant heart failure, or cardiorenal syndrome are described. The systems and methods are based on delivery of a chimeric natriuretic peptide to a patient. Methods for increasing peptide levels include direct peptide delivery via either an external or implantable programmable pump.

Claims

1. A medical system, comprising:

a drug provisioning component to administer a therapeutically effective amount of a chimeric natriuretic peptide to a subject suffering from kidney disease alone, heart failure alone, concomitant kidney disease and heart failure or cardiorenal syndrome, said drug provisioning component maintaining a plasma concentration of the chimeric natriuretic peptide within a specified range,

wherein the drug provisioning component administers the chimeric natriuretic peptide subcutaneously or intramuscularly.

2. The medical system of claim 1, wherein the chimeric natriuretic peptide is selected from any one of CD-NP (SEQ ID No. 3) and CU-NP (SEQ ID No. 4).

3. The medical system of claim 1, wherein the chimeric natriuretic peptide is selected from any one of SEQ ID No.'"'"'s 8-11.

4. The medical system of claim 1, wherein the drug provisioning component maintains a plasma level of the chimeric natriuretic peptide at a steady state concentration from any of from about 200 to about 1200 pg/mL, from about 250 to about 1000 pg/mL, from about 300 to about 900 pg/mL, from about 350 to about 800 pg/mL, from about 400 to about 600 pg/mL, from about 200 to 1200 pg/mL, from about 200 to about 800 pg/mL, from about 200 to about 1600 pg/mL and from about 400 to about 1600 pg/mL.

5. The medical system of claim 1, wherein the drug provisioning component delivers a therapeutically effective amount of the chimeric natriuretic peptide to maintain a plasma level of the chimeric natriuretic peptide (pg/mL) in the range represented by n to (n+i), where n={xε

Z|0<

x≦

1600} and i={yε

Z|0≦

y≦

(1600−

n)}.

6. The medical system of claim 1, wherein the drug provisioning component delivers a therapeutically effective amount of the chimeric natriuretic peptide to maintain a plasma level of the chimeric natriuretic peptide (pg/mL) in the range represented by n to (n+i), where n={xε

Z|0<

x≦

800} and i={yε

Z|0≦

y≦

(800−

n)}.

7. The medical system of claim 1, wherein the chimeric natriuretic peptide is administered to the subject at a rate from any one of about 1 to about 30 ng/(kg·

min), about 2 to about 25 ng/(kg·

min), about 5 to about 25 ng/(kg·

min), about 0.5 to about 20 ng/(kg·

min), and about 2.5 to about 25 ng/(kg·

min) of the subject'"'"'s body weight.

8. The medical system of claim 1, wherein the chimeric natriuretic peptide is administered to the subject at a rate from any one of about 6 to about 36 μ

g/hr, about 3 to about 6 μ

g/hr, from about 4 to about 5 μ

g/hr, from about 1 to about 10 μ

g/hr, from about 2 to about 8 μ

g/hr, from about 5 to about 30 μ

g/hr, from about 1 to about 36 μ

g/hr, from about 6 to about 10 μ

g/hr, about 6 to about 20 μ

g/hr and from about 5 to about 20 μ

g/hr.

9. The medical system of claim 1, wherein the drug provisioning component delivers a therapeutically effective amount of the chimeric natriuretic peptides at a rate (ng/kg of body weight) for 4 hours on and 8 hours off, then 4 hours on and 8 hours off for each of 3 days, wherein the rate results in a plasma concentration of the chimeric natriuretic peptides not greater than a plasma concentration of the chimeric natriuretic peptides reached in the subject during either a subcutaneous bolus at 1800 ng/kg or a 1 hour intravenous infusion of the chimeric natriuretic peptide at 30 ng/(kg·

min) based on the subject'"'"'s body weight.

10. The medical system of claim 1, wherein the drug provisioning component delivers a therapeutically effective amount of the chimeric natriuretic peptide in a cyclic on/off pattern at a rate (ng/kg of body weight) for multiple days, wherein the rate results in a plasma concentration of chimeric natriuretic peptide not greater than a plasma concentration of the chimeric natriuretic peptide reached in the subject during either a subcutaneous bolus at 1800 ng/kg or a 1 hour intravenous infusion of the chimeric natriuretic peptide at 30 ng/(kg·

min) based on the subject'"'"'s body weight.

11. The medical system of claim 1, wherein the drug provisioning component delivers a therapeutically effective amount of the chimeric natriuretic peptide in a cyclic on/off pattern at a rate (ng/(kg·

min)) for multiple days, wherein the rate is in a range represented by n to (n+i) where n={xε

Z|0<

x≦

30}and i={yε

Z|0≦

y≦

(30−

n)}.

12. The medical system of claim 1, wherein the drug provisioning component delivers a therapeutically effective amount of the chimeric natriuretic peptide in a cyclic on/off pattern at a rate (μ

g/hr) for multiple days, wherein the rate is in a range represented by n to (n+i) where n={xε

Z|0<

x≦

36}and i={yε

Z|0≦

y≦

(36−

n)}.

13. The medical system of claim 1, wherein the drug provisioning component delivers a therapeutically effective amount of the chimeric natriuretic peptide in a cyclic on/off pattern at a rate (ng/(kg·

min)) from about 2 to about 25 ng/(kg·

min), from about 5 to about 25 ng/(kg·

min), from about 0.5 to about 20 ng/(kg·

min), and from about 2.5 to about 25 ng/(kg·

min) based upon the subject'"'"'s body weight

14. The medical system of claim 1, wherein the drug provisioning component delivers a therapeutically effective amount of the chimeric natriuretic peptide at a continuous rate (ng/kg of body weight) matching the area under the curve of a subcutaneous bolus at 1800 ng/kg of the subject'"'"'s body weight.

15. The medical system of claim 1, further comprising a control unit in communication with the drug provisioning component.

16. The medical system of claim 1, wherein the drug provisioning component is selected from an external or implantable drug delivery pump, an implanted or percutaneous vascular access port, a direct delivery catheter system, and a local drug-release device.

17. The medical system of claim 16, wherein the drug provisioning component delivers the chimeric natriuretic peptide at a fixed, pulsed, continuous or variable rate.

18. The medical system of claim 16, wherein the drug provisioning component is programmable.

19. The medical system of claim 16, wherein the drug provisioning component is controlled by a patient who is the subject.

20. The medical system of claim 15, wherein the control unit comprises a processor and memory wherein the processor compiles and stores a database of data collected from the subject and computes a dosing schedule based on subject parameters.

21. The medical system of claim 20, wherein the dosing schedule is based on the subject'"'"'s body weight.

22. The medical system of claim 20, wherein the dosing schedule is adjusted based on pharmacokinetic variables.

23. The medical system of claim 22, wherein the pharmacokinetic variables are any one of area under the curve, clearance, volume of distribution, half-life, elimination rates, minimum inhibitory concentrations, route of administration, plasma concentrations of the chimeric natriuretic peptides, and rate of drug delivery.

24. The medical system of claim 1, wherein the data collected from the medical system is transmitted via radio frequency by a transmitter, and the data is received by an external controller.

25. The medical system of claim 1, wherein the data collected from the medical system is transmitted and digital instructions returned to the control unit via the Internet.

26. The medical system of claim 15, wherein the drug provisioning component and the control unit are co-located.

27. The medical system of claim 15, wherein the drug provisioning component or the control unit are connected or controlled wirelessly.

28. The medical system of claim 1, wherein the drug provisioning component is programmed to release a single bolus of 1800 ng of chimeric natriuretic peptide per kilogram of the subject'"'"'s body weight wherein the single bolus is administered three times at 0 hours, 24 hours and 48 hours.

29. The medical system of claim 1, wherein the drug provisioning component is programmed to continuously deliver 1800 ng per hour of chimeric natriuretic peptide per kilogram of the subject'"'"'s body weight over 72 hours.

30. The medical system of claim 1, further comprising a patch pump in communication with a control unit.

31. The medical system of claim 1, wherein kidney disease is selected from the group consisting of Stage 1 kidney disease, Stage 2 kidney disease, Stage 3 kidney disease, Stage 4, Stage 5 kidney disease, and end-stage renal disease.

32. The medical system of claim 1, wherein cardiorenal syndrome (CRS) is selected from the group consisting of CRS Type I, CRS Type II, CRS Type III, CRS Type IV and CRS Type V.

33. The medical system of claim 1, wherein heart failure is selected from the group consisting of chronic heart failure, congestive heart failure, acute heart failure, decompensated heart failure, systolic heart failure, and diastolic heart failure.

34. A method, comprising the steps of:

administering the chimeric natriuretic peptide to a subject suffering from kidney disease alone, heart failure alone, concomitant kidney disease and heart failure or cardiorenal syndrome using a drug provisioning component, and

maintaining a plasma concentration of the chimeric natriuretic peptide within a specified range,

wherein the drug provisioning component delivers the chimeric natriuretic peptide subcutaneously or intramuscularly.

35. The method of claim 34, wherein the chimeric natriuretic peptide is selected from any one of CD-NP (SEQ ID No. 3) or CU-NP (SEQ ID No. 4).

36. The method of claim 34, wherein the chimeric natriuretic peptide is selected from any one of SEQ ID No.'"'"'s 8-11.

37. The method of claim 34, wherein the drug provisioning component is selected from an external or implantable drug delivery pump, an implanted or percutaneous vascular access port, a direct delivery catheter system, and a local drug-release device.

38. The method of claim 34, wherein the drug provisioning component delivers the chimeric natriuretic peptide at a fixed, pulsed, continuous or variable rate.

39. The method of claim 34, wherein the specified range is not greater than a plasma concentration of the chimeric natriuretic peptide reached during either a subcutaneous bolus of the chimeric natriuretic peptide at 1800 ng/kg or a 1 hour intravenous infusion of the chimeric natriuretic peptide at 30 ng/kg·

min based on the subject'"'"'s body weight.

40. The method of claim 34, wherein the drug provisioning component delivers a therapeutically effective amount of the chimeric natriuretic peptide at a rate (ng/kg of body weight) for 4 hours on and 8 hours off, then 4 hours on and 8 hours off for each of 3 days, wherein the rate results in a plasma concentration of the chimeric natriuretic peptides not greater than a plasma concentration of the chimeric natriuretic peptide reached in the subject during either a subcutaneous bolus at 1800 ng/kg or a 1 hour intravenous infusion of the chimeric natriuretic peptide at 30 ng/(kg·

min) based on the subject'"'"'s body weight.

41. The method of claim 34, wherein the drug provisioning component delivers a therapeutically effective amount of the chimeric natriuretic peptide at a continuous rate (ng/kg of body weight) matching the area under the curve of a subcutaneous bolus at 1800 ng/kg based on the subject'"'"'s body weight.

42. The method of claim 34, further comprising the step of compiling and storing data collected from the subject using a processor and memory, and computing a dosing schedule.

43. The method of claim 34, further comprising the step of calculating the dosing schedule based on the subject'"'"'s body weight.

44. The method of claim 43, further comprising the step of adjusting the dosing schedule to meet pharmacokinetic variables calculated from one or more subject parameters.

45. The method of claim 44, wherein the pharmacokinetic variables are selected from any one of area under the curve, clearance, volume of distribution, half-life, elimination rates, minimum inhibitory concentrations, route of administration, plasma concentrations of the chimeric natriuretic peptide, and rate of drug delivery.

46. The method of claim 34, further comprising the step of collecting data from the drug provisioning component and transmitting the data via radio frequency to an external controller.

47. The method of claim 34, further comprising the step of collecting and transmitting data from the drug provisioning component and returning digital instructions to a control unit via the Internet.

48. The method of claim 34, wherein the drug provisioning component and a control unit are connected or controlled wirelessly.

49. The method of claim 34, wherein the drug provisioning component is programmed to release a single bolus of 1800 ng of chimeric natriuretic peptide per kilogram of the subject'"'"'s body weight.

50. The method of claim 49, wherein the single bolus is repeated three times.

51. The method of claim 34, wherein the drug provisioning component is programmed to continuously deliver 1800 ng per hour of chimeric natriuretic peptide per kilogram of the subject'"'"'s body weight.

52. The method of claim 34, wherein kidney disease is selected from the group consisting of Stage 1 kidney disease, Stage 2 kidney disease, Stage 3 kidney disease, Stage 4 kidney disease, Stage 5 kidney disease, and end-stage renal disease.

53. The method of claim 34, wherein cardiorenal syndrome (CRS) is selected from the group consisting of CRS Type I, CRS Type II, CRS Type III, CRS Type IV and CRS Type V.

54. The method of claim 34, wherein heart failure is selected from the group consisting of chronic heart failure, congestive heart failure, acute heart failure, decompensated heart failure, systolic heart failure, and diastolic heart failure.

55. A method for administering a chimeric natriuretic peptide to a subject suffering from kidney disease alone, heart failure alone, concomitant kidney disease and heart failure or cardiorenal syndrome, comprising:

administering the chimeric natriuretic peptide to the subject using a drug provisioning component to maintain a plasma level of the chimeric natriuretic peptide at a steady state concentration,

wherein the drug provisioning component administers the chimeric natriuretic peptide subcutaneously or intramuscularly.

56. The method of claim 55, wherein the steady state concentration is from about 0.5 to about 10 ng/mL.

57. The method of claim 55, wherein the plasma level of the chimeric natriuretic peptide is maintained at a steady state concentration range from any one of from about 200 to about 1200 pg/mL, from about 250 to about 1000 pg/mL, from about 300 to about 900 pg/mL, from about 350 to about 800 pg/mL, from about 400 to about 600 pg/mL, from about 200 to 1200 pg/mL, from about 200 to about 800 pg/mL, from about 200 to about 1600 pg/mL and from about 400 to about 1600 pg/mL.

58. The method of claim 55, wherein the plasma level of the chimeric natriuretic peptide (pg/mL) is maintained at a steady state concentration in the range represented by n to (n+i), where n={xε

Z|0<

x≦

1600} and i={yε

Z|0≦

y≦

(1600−

n)}.

59. The method of claim 55, wherein the plasma level of the chimeric natriuretic peptide (pg/mL) is maintained at a steady state concentration in the range represented by n to (n+i), where n={xε

Z|0<

x≦

800} and i={yε

Z|0≦

y≦

(800−

n)}.

60. The method of claim 55, wherein the chimeric natriuretic peptide is administered to the subject at a rate from any one of about 1 to about 30 ng/(kg·

min), about 2 to about 25 ng/(kg·

min), about 5 to about 25 ng/(kg·

min), about 0.5 to about 20 ng/(kg·

min), and about 2.5 to about 25 ng/(kg·

min) of the subject'"'"'s body weight.

61. The method of claim 55, wherein the chimeric natriuretic peptide is administered to the subject at a rate from any one of about 6 to about 36 μ

g/hr, about 3 to about 6 μ

g/hr, from about 4 to about 5 μ

g/hr, from about 1 to about 10 μ

g/hr, from about 2 to about 8 μ

g/hr, from about 5 to about 30 μ

g/hr, from about 1 to about 36 μ

g/hr, from about 6 to about 10 μ

g/hr, about 6 to about 20 μ

g/hr and from about 5 to about 20 μ

g/hr.

62. The method of claim 55, wherein the chimeric natriuretic peptide is administered to the subject in a cyclic on/off pattern at a rate (ng/kg of body weight) for multiple days, wherein the rate results in a plasma concentration of the chimeric natriuretic peptide not greater than a plasma concentration of the chimeric natriuretic peptide reached in the subject during either a subcutaneous bolus at 1800 ng/kg or a 1 hour intravenous infusion of the chimeric natriuretic peptide at 30 ng/(kg·

min) based on the subject'"'"'s body weight.

63. The method of claim 55, wherein the drug provisioning component delivers a therapeutically effective amount of the chimeric natriuretic peptide in a cyclic on/off pattern at a rate (ng/kg·

min) for multiple days, wherein the rate is in a range represented by n to (n+i) where n={xε

Z|0<

x≦

30}and i={yε

Z|0≦

y≦

(30−

n)}.

64. The method of claim 55, wherein the drug provisioning component delivers a therapeutically effective amount of the chimeric natriuretic peptide in a cyclic on/off pattern at a rate (μ

g/hr) for multiple days, wherein the rate is in a range represented by n to (n+i) where n={xε

Z|0<

x≦

36}and i={yε

Z|0≦

y≦

(36−

n)}.

65. The method of claim 55, wherein the drug provisioning component delivers a therapeutically effective amount of the chimeric natriuretic peptide in a cyclic on/off pattern at a rate (ng/(kg·

min)) from about 2 to about 25 ng/(kg·

min), from about 5 to about 25 ng/(kg·

min), from about 0.5 to about 20 ng/(kg·

min), and from about 2.5 to about 25 ng/(kg·

min) based upon the subject'"'"'s body weight.

66. The method of claim 55, wherein kidney disease is selected from the group consisting of Stage 1 kidney disease, Stage 2 kidney disease, Stage 3 kidney disease, Stage 4 kidney disease, Stage 5 kidney disease, and end-stage renal disease.

67. The method of claim 55, wherein heart failure is selected from the group consisting of chronic heart failure, congestive heart failure, acute heart failure, decompensated heart failure, systolic heart failure, and diastolic heart failure.

68. The method of claim 55, wherein cardiorenal syndrome (CRS) is selected from the group consisting of CRS Type I, CRS Type II, CRS Type III, CRS Type IV and CRS Type V.

69. A method for treating a subject suffering from kidney disease alone, heart failure alone, or with concomitant kidney disease and heart failure or cardiorenal syndrome, comprising:

administering a therapeutically effective amount of a chimeric natriuretic peptide to the subject by subcutaneous infusion, wherein the administration of the chimeric natriuretic peptide has one or more renal protective effects or cardiovascular effects.

70. The method of claim 69, wherein a therapeutically effective amount of the natriuretic peptide is administration at a rate (ng/kg of body weight) from any one of about 1 to about 30 ng/(kg·

min), about 2 to about 25 ng/(kg·

min), about 5 to about 25 ng/(kg·

min), about 0.5 to about 20 ng/(kg·

min), and about 2.5 to about 25 ng/(kg·

min) of the subject'"'"'s body weight.

71. The method of claim 69, wherein the chimeric natriuretic peptide is administered to the subject at a rate from any one of about 6 to about 36 μ

g/hr, about 3 to about 6 μ

g/hr, from about 4 to about 5 μ

g/hr, from about 1 to about 10 μ

g/hr, from about 2 to about 8 μ

g/hr, from about 5 to about 30 μ

g/hr, from about 1 to about 36 μ

g/hr, from about 6 to about 10 μ

g/hr, about 6 to about 20 μ

g/hr and from about 5 to about 20 μ

g/hr.

72. The method of claim 69, wherein the chimeric natriuretic peptide is selected from any one of CD-NP (SEQ ID No. 3) or CU-NP (SEQ ID No. 4).

73. The method of claim 69, wherein the chimeric natriuretic peptide is selected from any one of SEQ ID No.'"'"'s 8-11.

74. The method of claim 69, wherein the one or more cardiovascular protective effects includes lowering blood pressure or reducing an increase in blood pressure.

75. The method of claim 69, wherein the one or more renal protective effects includes slowing, abrogating, or reversing the decline in glomerular filtration rate.

76. The method of claim 69, wherein the one or more pharmacologic effects includes increasing cGMP excretion in urine.

79. The method of claim 69, wherein kidney disease is selected from the group consisting of Stage 1 kidney disease, Stage 2 kidney disease, Stage 3 kidney disease, Stage 4 kidney disease, Stage 5 kidney disease, and end-stage renal disease.

80. The method of claim 69, wherein cardiorenal syndrome (CRS) is selected from the group consisting of CRS Type I, CRS Type II, CRS Type III, CRS Type IV and CRS Type V.

81. The method of claim 69, wherein heart failure is selected from the group consisting of chronic heart failure, congestive heart failure, acute heart failure, decompensated heart failure, systolic heart failure, and diastolic heart failure.

77. The method of 69, wherein the one or more renal protective effects includes lowering the presence of albumin in urine or reducing an increase in albumin in urine.

78. The method of 69, wherein the one or more renal protective effects includes one or more selected from the group consisting of maintaining renal cortical blood flow and lowering the presence of protein in urine or reducing an increase in protein in urine.

82. A medical system, comprising:

a drug provisioning component to administer a therapeutically effective amount of a chimeric natriuretic peptide to a subject suffering from kidney disease alone, heart failure, concomitant kidney disease and heart failure or cardiorenal syndrome, said drug provisioning component maintaining a plasma concentration of the chimeric natriuretic peptide within a specified range,

wherein the drug provisioning component administers the chimeric natriuretic peptide subcutaneously or intramuscularly.

83. The medical system of claim 82, wherein the chimeric natriuretic peptide is selected from any one of CD-NP (SEQ ID No. 3) and CU-NP (SEQ ID No. 4).

84. The medical system of claim 82, wherein the drug provisioning component maintains a plasma level of the chimeric natriuretic peptide at a steady state concentration from any one of from about 200 to about 1200 pg/mL, from about 250 to about 1000 pg/mL, from about 300 to about 900 pg/mL, from about 350 to about 800 pg/mL, from about 400 to about 600 pg/mL, from about 200 to 1200 pg/mL, from about 200 to about 800 pg/mL, from about 200 to about 1600 pg/mL and from about 400 to about 1600 pg/mL.

85. The medical system of claim 82, wherein the drug provisioning component delivers a therapeutically effective amount of the chimeric natriuretic peptide to maintain a plasma level of the chimeric natriuretic peptide (pg/mL) at a steady state concentration in the range represented by n to (n+i), where n={xε

Z|0<

x≦

1600} and i={yε

Z|0≦

y≦

(1600−

n)}.

86. The medical system of claim 82, wherein the drug provisioning component delivers a therapeutically effective amount of the chimeric natriuretic peptide to maintain a plasma level of the chimeric natriuretic peptide (pg/mL) at a steady state concentration in the range represented by n to (n+i), where n={xε

Z|0<

x≦

800} and i={yε

Z|0≦

y≦

(800−

n)}.

87. The medical system of claim 82, wherein the administration rate is any one of about 6 to about 36 μ

g/hr, about 3 to about 6 μ

g/hr, from about 4 to about 5 μ

g/hr, from about 1 to about 10 μ

g/hr, from about 2 to about 8 μ

g/hr, from about 5 to about 30 μ

g/hr, from about 1 to about 36 μ

g/hr, from about 6 to about 10 μ

g/hr, about 6 to about 20 μ

g/hr and from about 5 to about 20 μ

g/hr.

88. The medical system of claim 82, wherein an administration rate of the chimeric natriuretic peptide is selected from any of from about 3 to about 10 ng/kg·

min, less than about 20 ng/kg·

min, from 1 to about 20 ng/kg·

min, from about 2 to about 20 ng/kg·

min, from about 3 to about 5 ng/kg·

min, and less than about 3.75 ng/kg·

min based about a weight of the subject, or selected from any of from about 3 to about 6 μ

g/hr, from about 4 to about 5 μ

g/hr, from about 1 to about 10 μ

g/hr, from about 2 to about 8 μ

g/hr, from about 5 to about 30 μ

g/hr, from about 1 to about 36 μ

g/hr and from about 5 to about 20 μ

g/hr.

89. The medical system of claim 82, wherein the specified range of plasma concentration is selected from any of from about 200 to about 1200 pg/mL, from about 250 to about 1000 pg/mL, from about 300 to about 900 pg/mL, from about 350 to about 800 pg/mL, from about 400 to about 600 pg/mL, from about 200 to 1200 pg/mL, from about 200 to about 800 pg/mL, from about 200 to about 1600 pg/mL, from about 500 to about 900 pg/mL, and from about 400 to about 1600 pg/mL.

90. The medical system of claim 82, wherein the drug provisioning component determines an administration rate of the chimeric natriuretic peptide at least in part by multiplying the square of the weight of the subject by a first coefficient to maintain the plasma concentration of the chimeric natriuretic peptide within the specified range.

91. The medical system of claim 82, wherein the drug provisioning component determines or adjusts an administration rate of the natriuretic peptide at least in part based on a quadratic function of weight of the subject, such that the plasma concentration of the natriuretic peptide is maintained at a concentration within the specified range.

92. The medical system of claim 82, wherein the drug provisioning component determines or adjusts an administration rate of the natriuretic peptide at least in part based on determining a plasma concentration of the natriuretic peptide at the end of a 24-hour period of subcutaneous infusion, wherein the plasma concentration of the natriuretic peptide at the end of a 24-hour period of subcutaneous infusion is determined from a linear combination of a quadratic function of weight of the subject and a linear function of the administration rate of the natriuretic peptide.

93. The medical system of claim 82, wherein the drug provisioning component determines an administration rate of the natriuretic peptide using the following formula:

94. The medical system of claim 82, wherein kidney disease is selected from the group consisting of Stage 1 kidney disease, Stage 2 kidney disease, Stage 3 kidney disease, Stage 4 kidney disease, Stage 5 kidney disease, and end-stage renal disease.

95. The medical system of claim 82, wherein heart failure is selected from the group consisting of chronic heart failure, congestive heart failure, acute heart failure, decompensated heart failure, systolic heart failure, and diastolic heart failure.

96. The medical system of claim 82, wherein cardiorenal syndrome (CRS) is selected from the group consisting of CRS Type I, CRS Type II, CRS Type III, CRS Type IV and CRS Type V.

97. A method, comprising the steps of:

administering a chimeric natriuretic peptide to a subject suffering from kidney disease alone, heart failure alone, concomitant kidney disease and heart failure or cardiorenal syndrome using a drug provisioning component, and

maintaining a plasma concentration of the chimeric natriuretic peptide within a specified range,

wherein the chimeric natriuretic peptide is administered subcutaneously or intramuscularly.

98. The method of claim 97, wherein an administration rate of the chimeric natriuretic peptide is determined at least in part based on adjusting an administration rate based upon a weight of the subject and/or a quadratic function of weight of the subject, such that the plasma concentration of the natriuretic peptide is maintained at a concentration within the specified range.

99. The method of claim 97, wherein an administration rate of the natriuretic peptide is determined using the following formula:

100. The method of claim 97, wherein an administration rate of the chimeric natriuretic peptide is selected from any of from about 3 to about 10 ng/kg·

min, less than about 20 ng/kg·

min, from 1 to about 20 ng/kg·

min, from about 2 to about 20 ng/kg·

min, from about 3 to about 5 ng/kg·

min, and less than about 3.75 ng/kg·

min based about a weight of the subject, or selected from any of from about 3 to about 6 μ

g/hr, from about 4 to about 5 μ

g/hr, from about 1 to about 10 μ

g/hr, from about 2 to about 8 μ

g/hr, from about 5 to about 30 μ

g/hr, from about 1 to about 36 μ

g/hr and from about 5 to about 20 μ

g/hr.

101. The method of claim 97, wherein the chimeric natriuretic peptide is selected from any one of CD-NP (SEQ ID No. 3) and CU-NP (SEQ ID No. 4).

102. The method of claim 97, wherein the chimeric natriuretic peptide is administered to maintain a plasma level of the chimeric natriuretic peptide (pg/mL) at a concentration in the range represented by n to (n+i), where n={xε

Z|0<

x≦

1600} and i={yε

Z|0≦

y≦

(1600−

n)}.

103. The method of claim 97, wherein the chimeric natriuretic peptide is administered to maintain a plasma level of the chimeric natriuretic peptide (pg/mL) at a concentration in the range represented by n to (n+i), where n={xε

Z|0<

x≦

800} and i={yε

Z|0≦

y≦

(800−

n)}.

104. The method of claim 97, wherein the specified range of plasma concentration is selected from any of about 200 to about 1200 pg/mL, from about 250 to about 1000 pg/mL, from about 300 to about 900 pg/mL, from about 350 to about 800 pg/mL,

105. The method of claim 97, wherein the specified range of plasma concentration is selected from any of about 400 to about 600 pg/mL, about 300 to about 900 pg/mL, from about 200 to 1200 pg/mL, from about 200 to about 800 pg/mL, from about 200 to about 1600 pg/mL and from about 400 to about 1600 pg/mL.

106. The method of claim 97, wherein the drug provisioning component determines an administration rate of the chimeric natriuretic peptide at least in part by multiplying the square of the weight of the subject by a first coefficient to maintain the plasma concentration of the chimeric natriuretic peptide within the specified range.

107. The method of claim 97, wherein an administration rate of the chimeric natriuretic peptide is from about 1.25 to about 2.5 ng/(kg·

min), based on the subject'"'"'s body weight, when administered within 24 hours of admission to a hospital where the subject is an acute heart failure patient.

108. The method of claim 97, wherein kidney disease is selected from the group consisting of Stage 1 kidney disease, Stage 2 kidney disease, Stage 3 kidney disease, Stage 4 kidney disease, Stage 5 kidney disease, and end-stage renal disease.

109. The method of claim 97, wherein cardiorenal syndrome (CRS) is selected from the group consisting of CRS Type I, CRS Type II, CRS Type III, CRS Type IV and CRS Type V.

110. The method of claim 97, wherein heart failure is selected from the group consisting of chronic heart failure, congestive heart failure, acute heart failure, decompensated heart failure, systolic heart failure, and diastolic heart failure.