Synthetic bifunctional molecules containing drug moiety and pharmacokinetic modulating moiety

• US 8,044,099 B2
• Filed: 12/13/2004
• Issued: 10/25/2011
• Est. Priority Date: 11/19/1999
• Status: Expired due to Fees

• Current Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford Management Co.)
• Original Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford Management Co.)
• Inventors: Wandless, Thomas J., Briesewitz, Roger, Crabtree, Gerald R.
• Primary Examiner(s): NAFF, DAVID M
• Application Number:
  US11/011,776
• Publication Number:
  US 20050209265A1
• Time in Patent Office: 2,507 Days
• Field of Search: None
• US Class Current: 514/569
• CPC Class Codes: A61K 47/54 the modifying agent being an organic compound
• CPC Class Codes: A61K 47/55 the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
• CPC Class Codes: Y10S 530/812 Peptides or proteins is immobilized on, or in, an organic carrier

Abstract

Bifunctional molecules and methods for their use are provided. The subject bifunctional molecules are conjugates of a drug moiety and a pharmacokinetic modulating moiety, where these two moieties are optionally joined by a linking group. The bifunctional molecules are further characterized in that they exhibit at least one modulated pharmacokinetic property upon administration to a host as compared to a free drug control. The subject bifunctional molecules find use in a variety of therapeutic applications.

Claims

1. A synthetic bifunctional molecule of less than about 5000 daltons consisting of a drug moiety and a pharmacokinetic modulating moiety, wherein said drug moiety and said pharmacokinetic modulating moiety are different and have been chosen so that said pharmacokinetic modulating moiety modulates at least one pharmacokinetic property of said drug moiety upon administration of said synthetic bifunctional molecule to a host as compared to a free drug control comprising said drug moiety, wherein said pharmacokinetic property is selected from the group consisting of half-life, hepatic first-pass metabolism, volume of distribution and degree of blood protein binding, and wherein the pharmacokinetic modulating moiety is selected from the group consisting of a ligand for α

-1 acid glycoprotein, sulfisoxazole and naproxen.

2. The bifunctional molecule according to claim 1, wherein said pharmacokinetic modulating moiety is a ligand for α

-1 acid glycoprotein.

3. The bifunctional molecule according to claim 2, wherein said pharmacokinetic modulating moiety is a small neutral or basic molecule.

4. The bifunctional molecule according to claim 3, wherein said pharmacokinetic modulating moiety selected from the group consisting of:

propanolol, chlorpromazine, dipyrimadole, metoclopromide, aprindine and verapamil.

5. The bifunctional molecule according to claim 1, wherein said pharmacokinetic modulating moiety is sulfisoxazole.

6. The bifunctional molecule according to claim 1, wherein said pharmacokinetic modulating moiety is naproxen.