Abuse-resistant amphetamine prodrugs

• US 7,687,466 B2
• Filed: 08/29/2008
• Issued: 03/30/2010
• Est. Priority Date: 02/22/2002
• Status: Expired due to Term

• Current Assignee: Takeda Pharmaceutical Company Limited
• Original Assignee: Shire LLC (Shire plc)
• Inventors: Piccariello, Thomas, Bishop, Barney, Krishnan, Suma, Verbicky, Christopher A., Oberlender, Robert, Mickle, Travis, Moncrief, James Scott, Lauderback, Christopher, Paul, Bernhard J.
• Primary Examiner(s): AUDET, MAURY A
• Application Number:
  US12/201,794
• Publication Number:
  US 20090131516A1
• Time in Patent Office: 578 Days
• Field of Search: 514/12, 514/2, 514/15, 514/44, 514/554, 530/300
• US Class Current: 514/17.5
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 47/542 Carboxylic acids, e.g. a fatty acid or an amino acid
• CPC Class Codes: A61P 15/10 for impotence
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/26 Psychostimulants, e.g. nicotine, cocaine
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 25/30 for treating abuse or dependence
• CPC Class Codes: A61P 25/34 Tobacco-abuse
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07C 237/06 having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
• CPC Class Codes: Y10S 436/901 Drugs of abuse, e.g. narcotics, amphetamine
• CPC Class Codes: Y10T 436/173845 : Amine and quaternary ammonium

Abstract

The invention describes compounds, compositions, and methods of using the same comprising a chemical moiety covalently attached to amphetamine. These compounds and compositions are useful for reducing or preventing abuse and overdose of amphetamine. These compounds and compositions find particular use in providing an abuse-resistant alternative treatment for certain disorders, such as attention deficit hyperactivity disorder (ADHD), ADD, narcolepsy, and obesity. Oral bioavailability of amphetamine is maintained at therapeutically useful doses. At higher doses bioavailability is substantially reduced, thereby providing a method of reducing oral abuse liability. Further, compounds and compositions of the invention decrease the bioavailability of amphetamine by parenteral routes, such as intravenous or intranasal administration, further limiting their abuse liability.

Claims

1. A pharmaceutical composition comprising (a) L-lysine-d-amphetamine or a pharmaceutically acceptable salt thereof and (b) a pharmaceutically acceptable additive.

2. A pharmaceutical composition as defined in claim 1, wherein said pharmaceutical composition is suitable for oral dosing.

3. A pharmaceutical composition as defined in claim 2, comprising from 2.5 mg to 500 mg of L-lysine-d-amphetamine or a pharmaceutically acceptable salt thereof.

4. A pharmaceutical composition as defined in claim 3, comprising from 10 mg to 250 mg of L-lysine-d-amphetamine or a pharmaceutically acceptable salt thereof.

5. A pharmaceutical composition as defined in claim 4, comprising from 25 mg to 75 mg of L-lysine-d-amphetamine or a pharmaceutically acceptable salt thereof.

6. A pharmaceutical composition as defined in claim 5, comprising 30 mg of L-lysine-d-amphetamine or a pharmaceutically acceptable salt thereof.

7. A pharmaceutical composition as defined in claim 5, comprising 50 mg of L-lysine-d-amphetamine or a pharmaceutically acceptable salt thereof.

8. A pharmaceutical composition as defined in claim 5, comprising 70 mg of L-lysine-d-amphetamine or a pharmaceutically acceptable salt thereof.

9. A pharmaceutical composition as defined in claim 2, comprising a salt of L-lysine-d-amphetamine.

10. A pharmaceutical composition as defined in claim 9, wherein said salt is a mesylate salt.

11. A pharmaceutical composition as defined in claim 10, wherein said salt is a dimesylate salt.

12. A pharmaceutical composition comprising L-lysine-d-amphetamine dimesylate and a pharmaceutically acceptable additive, wherein said pharmaceutical composition has a water content of about 1% to about 10% by Karl Fischer analysis.

13. A pharmaceutical composition as defined in claim 12, wherein said pharmaceutical composition has a water content of about 1% to about 8% by Karl Fischer analysis.

14. A pharmaceutical composition as defined in claim 13, wherein said water content is about 2% to about 7% by Karl Fischer analysis.