Methods for administration and formulations for the treatment of regional adipose tissue
Provided herein are pharmaceutical formulations, methods, and systems for treating regional fat deposits and fat-related conditions and indications. Methods comprise administering a pharmaceutical formulation consisting essentially of a long-acting beta-2 adrenergic receptor agonist, for example, salmeterol, suitable for subcutaneous administration. Methods further comprise administering a pharmaceutical formulation that is suitable for subcutaneous injection comprising: (a) a lipophilic long-acting selective beta-2 adrenergic receptor agonist and/or glucocorticosteroid, or a salt, optical isomer, racemate, solvate, or polymorph thereof; and (b) at least one subcutaneously acceptable inactive ingredient.
1. An aqueous formulation comprising a formulation suitable for subcutaneous injection that comprises an adipose tissue-reducing lipophilic long-acting selective beta-2 adrenergic receptor agonist or a salt thereof that is formulated as a single session dose of up to 5 micrograms of the agonist that is free of copolymer, and at least one subcutaneously acceptable aqueous inactive ingredient; wherein the lipophilic long-acting selective beta-2 adrenergic receptor agonist is salmeterol, formoterol, bambuterol, or a salt thereof.
2. The formulation of claim 1 , wherein the lipophilic long-acting selective beta-2 adrenergic receptor agonist is salmeterol xinafoate.
3. The formulation of claim 2 , wherein the formulation provides a mean blood plasma C max of salmeterol xinafoate that is equal to or less than about 300 picograms/mL when administered to a subject.
4. The formulation of claim 1 , wherein the lipophilic long-acting selective beta-2 adrenergic receptor agonist selectively partitions into adipose tissue relative to blood plasma when administered to a subject.
5. The formulation of claim 4 , provides a partition ratio of from about 0.01 to about 0.2 when the lipophilic long-acting selective beta-2 adrenergic receptor agonist is administered subcutaneously.
6. The formulation of claim 2 , wherein the formulation provides a partition ratio of the lipophilic long-acting selective beta-2 adrenergic receptor agonist that is at least about four times lower than the partition ratio of formoterol.
7. The formulation of claim 1 , further comprising a co-solvent.
8. The formulation of claim 7 , wherein the co-solvent is selected from polyethylene glycol and polysorbate, and combinations thereof.
9. The formulation of claim 1 , wherein the dose is divided into one or more sub-doses.
10. A method of reducing adipose tissue in a patient comprising subcutaneously administering an aqueous formulation suitable for subcutaneous injection comprising: an adipose tissue-reducing lipophilic long-acting selective beta-2 adrenergic receptor agonist or a salt thereof that is formulated as a single session dose of up to 5 micrograms of the agonist that is free of copolymer and that is suitable for subcutaneous injection; and at least one subcutaneously acceptable inactive ingredient; wherein the lipophilic long-acting selective beta-2 adrenergic receptor agonist is salmeterol, formoterol, bambuterol, or a salt thereof.
11. The method of claim 10 , wherein the lipophilic long-acting selective beta-2 adrenergic receptor agonist is administered to a patient in a weekly dose that is between about 5 nanograms to about 5 micrograms.
12. The method of claim 10 , wherein the lipophilic long-acting selective beta-2 adrenergic receptor agonist is salmeterol, formoterol, or a salt thereof.
13. The method of claim 10 , wherein the circumference of the patient's abdomen is reduced by at least two centimeters when assessed by tape measure.
14. The method of claim 13 , wherein the two centimeter reduction in the patient's waist is evident at anytime between 4 and 8 weeks from the first day of treatment.