COLCHICINE PRODUCTS, METHOD OF MANUFACTURE, AND METHODS OF USE

• US 20090318561A1
• Filed: 06/23/2009
• Published: 12/24/2009
• Est. Priority Date: 06/23/2008
• Status: Abandoned Application

• Current Assignee: Takeda Pharmaceuticals USA Incorporated (Takeda Pharmaceutical Company Limited)
• Original Assignee: Mutual Pharmaceutical Co Inc (Takeda Pharmaceutical Company Limited)
• Inventors: Davis, Matthew W., Du, Jie, Nielsen, Kurt R., Roberts, Richard H.
• Application Number:
  US12/489,750
• Publication Number:
  US 20090318561A1
• Time in Patent Office: Days
• US Class Current: 514/625
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61P 19/06 Antigout agents, e.g. antihyperuricemic or uricosuric agents
• CPC Class Codes: G16H 40/63 for local operation
• CPC Class Codes: G16H 70/40 relating to drugs, e.g. their side effects or intended usage

Abstract

Disclosed herein is a method of using colchicine. In one embodiment, the method comprises administering to a patient colchicine and a substrate of cytochrome P450 1A2 and monitoring the patient during administration of colchicine and the substrate for an adverse event. Also disclosed are articles of manufacture comprising a container containing a dosage form of colchicine and a method of manufacturing a colchicine product.

Claims

1. A method of determining risk of an adverse event in administration of colchicine comprising

determining for a patient to whom colchicine is going to be administered or is being administered whether a substance that is currently being or will be administered to the patient is a substrate of CYP1A2;

and

determining risk for the patient of an adverse event during coadministration of colchicine and the substance resulting from reduced metabolism of the substance by CYP1A2.

2. The method of claim 1, comprising

determining risk for the patient of an adverse event during coadministration of colchicine and the substance resulting from reduced metabolism of the substance by CYP1A2,

wherein the reduced metabolism of the substance by CYP1A2 is due to down-regulation of CYP1A2 expression by colchicine.

3. The method of claim 1, wherein determining risk comprises

accessing a pharmacy management system.

4. The method of claim 1, further comprising

administering colchicine to the patient with the substance if there is not a risk of an adverse event.

5. The method of claim 1, further comprising

administering colchicine to the patient with the substance if risk of an adverse event is determined to be acceptable.

6. The method of claim 1, further comprising

administering colchicine to the patient but not administering the substance if there is a risk of an adverse event.

7. The method of claim 1, comprising

administering colchicine to the patient but not administering the substance if there is an unacceptable risk of an adverse event.

8. The method of claim 1, wherein the patient has gout or an attack of acute gouty arthritis.

9-10. -10. (canceled)

11. A method of coadministration of colchicine and a substrate of CYP1A2 to a patient comprising,

administering colchicine and a substrate of CYP1A2 to a patient in need of colchicine and the substrate;

monitoring the patient during coadministration of the colchicine and the substrate; and

adjusting the dosing of colchicine or the substrate in response to the monitoring such that an adverse event associated with the coadministration of colchicine and a substrate of CYP1A2 is avoided.

12. The method of claim 11, wherein monitoring the patient comprises

monitoring the patient'"'"'s plasma concentration of the substrate;

monitoring the patient for an adverse reaction associated with elevated substrate plasma concentration;

monitoring the patient for a symptom of an active agent interaction between the substrate and colchicine;

monitoring the patient for an adverse reaction resulting from coadministration of the substance and the substrate;

monitoring the patient for an adverse reaction or side effect associated with the substrate;

monitoring the patient for a substrate-associated toxicity;

or

monitoring the patient for a symptom of elevated plasma concentration of the substrate.

13. The method of claim 11, wherein the patient has acute gouty arthritis;

chronic gout;

a cystic disease comprising polycystic kidney disease or cystic fibrosis;

a lentiviral infection;

a demyelinating disease of central or peripheral origin;

multiple sclerosis;

cancer;

an inflammatory disorder comprising rheumatoid arthritis;

glaucoma;

Dupuytren'"'"'s contracture;

idiopathic pulmonary fibrosis;

primary amyloidosis;

recurrent pericarditis;

acute pericarditis;

asthma;

postpericardiotomy syndrome;

proliferative vitreoretinopathy;

Behç

et'"'"'s disease;

Familial Mediterranean fever;

idiopathic thrombocytopenic purpura;

primary biliary cirrhosis;

or pyoderma gangrenosum;

or is in need of enhanced bone mineral density.

14-32. -32. (canceled)

33. A method of administering colchicine to a patient in need thereof, comprising

receiving information that colchicine

a) is metabolized by cytochrome P450 2A6, 2B6, 2C8, 2C9 or 2C19;

b) inhibited cytochrome P450 2A6 or 2C8 enzyme activity in an in vitro inhibition study;

c) activated CYP3A4 enzyme activity in an in vitro inhibition study;

d) suppressed enzyme activity of cytochrome P450 1A2, 2A6, 2C19, 2D6, or 2E1 in an in vitro induction study;

or

e) suppressed mRNA expression of cytochrome P450 1A2 in an in vitro induction study;

and

adjusting administration of colchicine and an active agent to a patient in response to the information to avoid an adverse event in the patient.

34. The method of claim 33, wherein the method further comprises

informing the patient or the patient'"'"'s medical care worker that administration of colchicine with an active agent that is a known substrate of cytochrome P450 1A2, 2A6, 2C19, 2D6, or 2E1 can result in reduced metabolism of the active agent or increased plasma concentration of the active agent;

or

monitoring the patient during administration of colchicine.

35. The method of claim 34, wherein monitoring the patient comprises:

monitoring the patient'"'"'s plasma concentration of the active agent or colchicine;

monitoring the patient for symptoms of an active agent interaction between the active agent and colchicine;

monitoring the patient for an adverse event associated with elevated plasma concentration of the active agent;

or

monitoring the patient for an adverse reaction or side effect resulting from coadministration of the active agent and colchicine.

36-45. -45. (canceled)