Breath test for detection of drug metabolism

• US 6,180,414 B1
• Filed: 06/28/1999
• Issued: 01/30/2001
• Est. Priority Date: 01/03/1997
• Status: Expired due to Term

• Current Assignee: Oridion Medical (1987) Ltd. (Medtronic Plc)
• Original Assignee: Oridion Medical (1987) Ltd. (Medtronic Plc)
• Inventors: Katzman, Daniel E.
• Primary Examiner(s): WALLENHORST, MAUREEN
• Application Number:
  US09/340,546
• Time in Patent Office: 582 Days
• Field of Search: 436/56, 436/106, 436/108, 436/113, 436/127, 436/133, 436/173, 436/175, 436/181, 436/900, 422/61, 422/83, 422/84, 73/233
• US Class Current: 436/181
• CPC Class Codes: A61K 47/6949 inclusion complexes, e.g. clathrates, cavitates or fullerenes
• CPC Class Codes: A61K 51/1206 Administration of radioactive gases, aerosols or breath tests
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: Y10S 436/90 Breath testing
• CPC Class Codes: Y10T 436/13 Tracers or tags
• CPC Class Codes: Y10T 436/204998 Inorganic carbon compounds
• CPC Class Codes: Y10T 436/24 Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry
• CPC Class Codes: Y10T 436/25875 Gaseous sample or with change of physical state

Abstract

A breath test for determining the rate of metabolism of a drug is described. First, a safe and effective amount of the drug, preferably appropriately labelled and most preferably isotopically-labelled, is administered to a subject. After a suitable time period, the exhaled breath of the subject is analyzed to determine the concentration of a metabolite. The concentration of the metabolite is then used to determine the rate of metabolism of the drug. A breath test kit is also described. Such a breath test kit would include an item or items necessary for performing at least one of the methods of determining the rate of metabolism of a drug in a subject. For example, such a breath test kit could include an isotopically-labelled drug to be administered to the subject.

Claims

1. A method for measuring a characteristic of metabolism of a drug of therapeutic value to a subject and determining a therapeutically effective dosage of said drug for said subject, the characteristic of metabolism being selected from a group consisting of a rate of metabolism and an extent of metabolism, the method comprising the steps of:

(a) administering said drug labeled with an isotope to said subject, such that said drug is an administered drug;

(b) analyzing exhaled breath of the subject for a concentration of said isotope, said concentration of said isotope directly indicating the characteristic of metabolism of said administered drug in the subject and (C) employing said characteristic of metabolism to determine a therapeutically effective dosage of said drug for said subject.

2. The method of claim 1, wherein said exhaled breath of the subject is analyzed by a measuring instrument selected from the group consisting of an infrared spectrometer and a mass spectrometer.

3. The method of claim 1, wherein said exhaled breath contains carbon dioxide.

4. The method of claim 3, wherein said carbon dioxide is isotopically-labeled with an isotope selected from the group consisting of carbon-13, carbon-14 and oxygen-18.

5. The method of claim 1, wherein said exhaled breath contains ammonia.

6. The method of claim 5, wherein said ammonia is nitrogen-15 isotopically-labeled.

7. The method of claim 1, wherein said exhaled breath contains a substantially unchanged form of the drug.

8. The method of claim 7, wherein said exhaled breath is isotopically labeled with an isotope selected from the group consisting of carbon-13, carbon-14, nitrogen-15 and oxygen-18.

9. The method of claim 1, further comprising the step of analyzing a reference sample of said exhaled breath of the subject, said reference sample being obtained substantially before the drug is administered to the subject.

10. The method according to claim 7 wherein said isotope is nitrogen-15.

11. The method according to claim 10 wherein the analyzing step comprises using a measuring instrument selected from the group consisting of an infrared spectrometer and a mass spectrometer.

12. The method according to claim 10 wherein the metabolism characteristic is related to the amount of carbon dioxide labeled with said isotope.

13. The method according to claim 10 wherein said isotope is selected from the group consisting of carbon-13, carbon-14 and oxygen-18.

14. The method according to claim 10 wherein the metabolism characteristic is related to the amount of ammonia labeled with said isotope.

15. The method according to claim 14 wherein said isotope is nitrogen-15.

16. The method according to claim 10 wherein the metabolism characteristic is related to the amount of a substantially unchanged form of the drug labeled with said isotope.

17. The method according to claim 14 wherein said isotope is nitrogen-15.

18. The method according to claim 10 wherein the step of analyzing also comprises analysis of a reference sample of the exhaled breath of the subject, said reference sample being taken prior to the step of administration of the drug.

19. A method for measuring a rate of metabolism of a drug of therapeutic value to a subject and determining a therapeutically effective dosages of said drug for said subject, comprising:

(a) administering said drug labeled with an isotope to said subject, such that said drug is an administered drug;

(b) analyzing exhaled breath of the subject for a concentration of said isotope, said concentration of said isotope directly indicating the rate of metabolism of the administered drug in said subject and

(c) employing said rate of metabolism to determine a therapeutically effective dosage of said drug for said subject.

20. The method according to claim 19 wherein the analyzing step comprises using a measuring instrument selected from the group consisting of an infrared spectrometer and a mass spectrometer.

21. The method according to claim 19 wherein the rate of metabolism is related to the amount of carbon dioxide labeled with said isotope.

22. The method according to claim 19 wherein said isotope is selected from the group consisting of carbon-13, carbon-14 and oxygen-18.

23. The method according to claim 19 wherein the rate of metabolism is related to the amount of ammonia labeled with said isotope.

24. The method according to claim 23 wherein said isotope is nitrogen-15.

25. The method according to claim 19 wherein the rate of metabolism is related to the amount of a substantially unchanged form of the drug labeled with said isotope.

26. The method according to claim 25 wherein said isotope is selected from the group consisting of carbon-13, carbon-14, nitrogen-15 and oxygen-18.

27. The method according to claim 19 wherein the step of analyzing also comprises analysis of a reference sample of the exhaled breath of the subject.