Compositions and methods of administering baclofen
View Patent ↗Injectable baclofen formulations and methods that are bioequivalent in terms of plasma baclofen exposure to oral dosage forms but with reduced exposure ratios of baclofen to the M1 metabolite.
1. A method of treating spasticity in a patient comprising:
administering by intramuscular injection to the patient a pharmaceutical formulation comprising:
an effective amount of 4-amino-3-(4-chlorophenyl)butanoic acid) (baclofen), and one or more pharmaceutically acceptable excipients; wherein
the formulation is an injectable formulation at a concentration of 4 mg/mL baclofen; and wherein
on administration to a patient produces 3-(4-chlorophenyl)-4-hydroxybutyric acid (M1) as a metabolite in the patient; wherein
a ratio C max(baclofen) :C max(M1) is A, and AUC (0-t)(baclofen) :AUC (0-t)(M1) is B; and wherein
administering the pharmaceutical formulation to the patient produces A and B values that are more than 10% higher than a ratio C max(baclofen) :C max(M1) and a ratio AUC (0-t)(baclofen) :AUC (0-t)(M1) for a baclofen tablet formulation according to Baclofen Tablets monograph as defined by US Pharmacopeia and containing an equal amount of baclofen,
wherein intramuscularly administering a 20-mg dose of the formulation to the patient produces a C max(baclofen) value of from about 257 ng/mL to about 478 ng/mL.
2. The method according to claim 1 , wherein intramuscularly administering a 20-mg dose of the formulation to the patient produces a C (max)(M1) value of from about 30 ng/mL to about 57 ng/mL.
3. The method of claim 1 , wherein intramuscularly administering a 20-mg dose of the formulation to the patient produces a ratio C max(baclofen) :C max(M1) of from about 4.5 to about 15.9.
4. The method of claim 3 , wherein intramuscularly administering a 20-mg dose of the formulation to the patient produces a ratio C max(baclofen) :C max(M1) of from about 8.0 to about 15.9.
5. The method of claim 1 , wherein intramuscularly administering a 20-mg dose of the formulation to the patient produces a ratio C max(baclofen) :C max(M1) of from about 8.5 to about 15.9.
6. The method according to claim 1 , wherein intramuscularly administering a 20-mg dose of the formulation to the patient produces a AUC (0-t)(baclofen) value of from about 2017 h·ng/mL to about 2821 h·ng/mL.
7. The method according to claim 1 , wherein intramuscularly administering a 20-mg dose of the formulation to the patient produces a AUC (0-t)(M1) value of from about 399 h·ng/mL to about 896 h·ng/mL.
8. The method of claim 1 , wherein intramuscularly administering a 20-mg dose of the formulation to the patient produces a ratio AUC (0-t)(baclofen) :AUC (0-t)(M1) of from about 2.3 to about 7.1.
9. The method of claim 8 , wherein intramuscularly administering a 20-mg dose of the formulation to the patient produces a ratio AUC (0-t)(baclofen) :AUC (0-t)(M1) of from about 3.5 to about 7.1.
10. The method of claim 9 , wherein intramuscularly administering a 20-mg dose of the formulation to the patient produces a ratio AUC (0-t)(baclofen) :AUC (0-t)(M1) of from about 3.8 to about 7.1.
11. The method of claim 1 , wherein the spasticity results from multiple sclerosis.
12. The method of claim 1 , wherein the spasticity is associated with at least one of flexor spasms, pain, clonus, and muscular rigidity.
13. The method of claim 1 , wherein the effective amount of baclofen is 20 mg.
14. The method of claim 1 , wherein the spasticity results from cerebral palsy, stroke, traumatic brain injury, spinal cord injury, spinal cord disease, or combinations thereof.