Modulation of drug effects by vagus nerve stimulation

• US 7,706,875 B2
• Filed: 01/25/2007
• Issued: 04/27/2010
• Est. Priority Date: 01/25/2007
• Status: Active Grant

• Current Assignee: LivaNova USA, Inc. (LivaNova Plc)
• Original Assignee: Cyberonics, Inc
• Inventors: Farroni, Jeffrey S., Buras, William R.
• Primary Examiner(s): Manuel; George
• Assistant Examiner(s): Wieland; Robert N
• Application Number:
  US11/698,226
• Publication Number:
  US 20080183226A1
• Time in Patent Office: 1,188 Days
• Field of Search: 607/2, 607/40, 607/127, 607/119, 424/158.1, 623/1.11, 623/1.15, 623/1.16
• US Class Current: 607/2
• CPC Class Codes: A61N 1/36114 Cardiac control, e.g. by vagal stimulation stimulating the heart A61N1/362

Abstract

A method of treating a patient undergoing pharmacotherapy with a selected drug for treatment of a medical disorder is provided which comprises: (a) administering the selected drug to said patient at a first time point, to treat the medical disorder; and (b) applying an electrical signal to a vagus nerve of the patient at a second time point, wherein the signal is selected so as to modulate at least one pharmacologic and/or pharmacokinetic property of the selected drug in the body of the patient. The vagus nerve stimulation (VNS) modulated drug therapy may be performed secondarily to, and in conjunction with, application of a primary VNS therapy to the patient for treatment of the same or a different medical disorder, to enhance treatment of the patient.

Claims

1. A method of treating a patient undergoing pharmacotherapy with a selected drug for treatment of a medical disorder, the method comprising:

administering the selected drug to said patient at a first time point to treat said medical disorder; and

applying a first electrical signal to a vagus nerve of the patient at a second time point,

wherein said first electrical signal is selected so as to modulate at least one pharmacologic and/or pharmacokinetic property of the selected drug in the body of the patient, wherein said at least one property is selected from the group consisting of the rate of intestinal absorption of said drug or a biologically active metabolite thereof, plasma binding of said drug, solubility of said drug in a body fluid, volume of distribution of said drug, and clearance of said drug, and

wherein said second time point is selected from the group consisting of a selected time before said first time point, a selected time after said first time point, and a selected time in the patient'"'"'s circadian rhythm after said first time point.

2. The method of claim 1, wherein administering said drug to the patient comprises administering a therapeutically effective reduced dosage of said drug compared to the dosage that would be administered to the patient in the absence of applying said first electrical signal to said vagus nerve.

3. The method of claim 1, wherein said modulating results in an increased therapeutic index of said drug.

4. The method of claim 1, wherein applying said first electrical signal to said vagus nerve comprises applying said first signal to a vagus nerve site in the cervical region of the patient.

5. The method of claim 1, wherein applying said first electrical signal to said vagus nerve comprises applying said first signal to at least one site on said vagus nerve in the supra-diaphragmatic thoracic region of the patient.

6. The method of claim 1, wherein applying said first electrical signal to said vagus nerve comprises applying said first signal to at least one site on said vagus nerve in the sub-diaphragmatic abdominal region of the patient.

7. The method of claim 1, wherein administering said drug to said patient comprises administering said drug immediately before applying said first electrical signal to said vagus nerve.

8. The method of claim 1, wherein said second time point is a predetermined interval of time after said first time point.

9. The method of claim 1, wherein administering said drug to said patient comprises chronic administration of said drug to said patient, and wherein applying said first electrical signal comprises repeatedly applying said electrical signal at a predetermined series of time intervals after said first time point.

10. The method of claim 1, wherein said method further comprises applying a second electrical signal, different from said first electrical signal, to a vagus nerve of the patient, wherein said second electrical signal is selected so as to treat a medical condition of a patient independent of the effects of said drug.

11. The method of claim 1, wherein said at least one pharmacologic and/or pharmacokinetic property comprises the rate of intestinal absorption of the selected drug, or a biologically active metabolite thereof

12. The method of claim 1, wherein said at least one pharmacologic and/or pharmacokinetic property comprises a property selected from the group consisting of plasma binding of the selected drug, solubility of said drug in a body fluid, volume of distribution of said drug, and clearance of said drug.

13. The method of claim 1, wherein applying said first electrical signal to a vagus nerve comprises modulation of the hypothalamus area of the patient'"'"'s brain.

14. The method of claim 1, wherein applying said first electrical signal to a vagus nerve comprises modulation of the brainstem area of the patient'"'"'s brain.

15. The method of claim 1, wherein applying said first electrical signal to said vagus nerve comprises modulation of the function of an organ selected from the group consisting of the stomach, the pancreas, the liver, the lungs, the intestines, and the kidneys.

16. The method of claim 1, wherein applying said first electrical signal to said vagus nerve comprises applying said signal to a main branch of the left or right vagus nerves, or to a branch of the vagus nerve connecting a main branch of the vagus nerve to an organ selected from the group consisting of the stomach, the pancreas, the liver, the lungs, the intestines and the kidneys.

17. The method of claim 1, wherein applying said first electrical signal to said vagus nerve comprises applying said signal to an electrically conductive tissue adjacent to the vagus nerve to indirectly apply said first electrical signal to said vagus nerve.

18. A method of enhancing treatment of a patient undergoing pharmacotherapy with a predetermined dosage of a selected drug for treatment of a medical disorder, the method comprising:

(a) administering a first predetermined dosage of said drug to the patient;

(b) applying a first electrical signal to at least one site on a left or right vagus nerve of the patient, wherein said first electrical signal is selected so as to modulate at least one pharmacologic and/or pharmacokinetic property of the selected drug in the body of the patient, wherein said at least one property is selected from the group consisting of the rate of intestinal absorption of said drug or a biologically active metabolite thereof, plasma binding of said drug, solubility of said drug in a body fluid, volume of distribution of said drug, and clearance of said drug;

(c) determining from the resulting modulation of said at least one property an increase or decrease in the efficacy of said drug; and

(d) decreasing the drug dosage to enhance treatment of said patient for said disorder if the resulting modulation increases the efficacy of said drug.

19. A method of enhancing treatment of a patient undergoing therapeutic vagus nerve stimulation for a medical disorder, comprising:

(a) applying a first electrical signal to a site on a vagus nerve of the patient, wherein said first electrical signal is selected so as to therapeutically treat said medical disorder;

(b) administering a drug therapy to said patient for the same or a different medical disorder; and

(c) applying a second electrical signal to a site on a vagus nerve, wherein said second electrical signal is selected to modulate at least one pharmacologic and/or pharmacokinetic property of the selected drug in the body of the patient, said at least one property being selected from the group consisting of the rate of intestinal absorption of said drug or a biologically active metabolite thereof, plasma binding of said drug, solubility of said drug in a body fluid, volume of distribution of said drug, and clearance of said drug, to enhance said drug therapy.

20. The method of claim 19, wherein said second electrical signal is applied to a site on a vagus nerve that is different from the site where said first electrical signal is applied.

21. The method of claim 19, wherein said second electrical signal is applied during off-times of said first electrical signal.

22. The method of claim 19, wherein applying said second electrical signal causes enhancement of at least one of bioavailability, efficacy and safety of said drug.

23. The method of claim 19, wherein said first electrical signal, said drug, and said second electrical signal are selected to synergistically enhance treatment of said medical disorder.