Rapid establishment and/or termination of substantial steady-state drug delivery

摘要

The disclosure relates to the use of an exenatide for the manufacture of a medicament for treating type 2 diabetes mellitus and obesity a human by a method comprising: providing continuous delivery of the exenatide from an osmotic delivery device comprising: (1) an impermeable reservoir comprising interior and exterior surfaces and first and second open ends; (2) a semi-permeable membrane in sealing relationship with the first open end of the reservoir; (3) an osmotic engine within the reservoir and adjacent the semi-permeable membrane; (4) a piston adjacent the osmotic engine, wherein the piston forms a movable seal with the interior surface of the reservoir and divides the reservoir into a first chamber and a second chamber, the first chamber comprising the osmotic engine and the second chamber comprising a suspension formulation; and (5) a diffusion moderator inserted in the second open end of the reservoir, the diffusion moderator adjacent the suspension formulation, the suspension formulation comprising a particle formulation and a vehicle formulation, the particle formulation comprising particles comprising exenatide in particles of less than 10 microns in diameter and the vehicle formulation comprising: a solvent selected from the group consisting of benzyl benzoate, lauryl lactate, and lauryl alcohol, and (b) a polymer that is polyvinylpyrrolidone, the vehicle formulation having a viscosity between about 10,000 poise and about 20,000 poise at 37 degrees Celsius; wherein substantial steady-state delivery of the exenatide at a therapeutic concentration is achieved within a time period of 5 days or less after implantation of the osmotic delivery device in the human and the substantial steady-state delivery of the exenatide from the osmotic delivery device is continuous over an administration period of at least 3 months at a mcg/day dose of the exenatide selected from the group consisting of about 10 mcg/day, about 20 mcg/day, about 30 mcg/day, about 40 mcg/day, about 60 mcg/day, and about 80 mcg/day.