Method for increasing the bioavailability of metaxalone

Details Method for increasing the bioavailability of metaxalone Method for increasing the bioavailability of metaxalone

2001-12-03

2002-06-18

Henley, III, Raymond (Department: 1614)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

Reexamination Certificate

active

06407128

ABSTRACT:

FIELD OF THE INVENTION
The invention relates to methods for increasing the bioavailability of a medicinal agent, namely metaxalone (5-[(3,5-dimethylphenoxy)methyl]-2 oxazolidinone).
BACKGROUND OF THE INVENTION
Metaxalone (Skelaxin®) has the following chemical structure and name:
5-[(3,5 -dimethylphenoxy)methyl]-2 oxazolidinone
Skelaxin is indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomforts associated with acute, painful musculoskeletal conditions. The mode of action of this drug has not been clearly identified, but may be related to its sedative properties. Metaxalone does not directly relax tense skeletal muscles in man. The commercially available tablet contains: metaxalone, 400 mg along with inert compression tableting excipients.
Metaxalone is further described at Monograph no. 5838 of the Merck Index (Eleventh Addition, Merck & Co., 1989) and is also identified by CAS Registry Number: 1665-48-1. It is also known by the drug code, AHR-438; and the drug product containing it is marketed as Skelaxin® (a trademark of Elan Pharmaceuticals, Inc.).
Preparation of metaxalone is described in Lunsford et al., J. Am. Chem. Soc. 82, 1166 (1960) and U.S. Pat. No. 3,062,827 to Lunsford Nov. 6, 1962 Assignee A. H. Robins), which is incorporated herein in its entirety by reference. The '827 patent discloses the compound and related species as anticonvulsants and antispasmodics, however, these activities have not been borne out by clinical experience.
Metaxalone is a central nervous system depressant that has sedative and skeletal muscle relaxant effects. Metaxalone is indicated as an adjunct to rest, physical therapy and other measures for the relief of discomforts associated with acute, painful muscoloskeletal conditions. See Skelaxin® monograph, 2001 Physicians' Desk Reference®, Medical Economics Company, Inc. (publisher) Montvale, N.J.
The most frequent reactions to metaxalone include nausea, vomiting, gastrointestinal upset, drowsiness, dizziness, headache, and nervousness or “irritability.” Other adverse reactions are: hypersensitivity reaction, characterized by a light rash with or without pruritus; leukopenia; hemolytic anemia; jaundice.
Pharmacokinetic studies have not previously been conducted to date to evaluate the effect of food on the pharmacokinetics of metaxalone. The hydrophobicity of the metaxalone molecule and the dosage amount required for a therapeutic effect both point to probably limited absorption from the gut when administered orally. More oral bioavailability of the drug substance has been sought to increase both speed of onset and amount of therapeutic effect.


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Monograph No. 5838 of the Merck Index (11thed., 1989) for metaxalone.
Lunsford et al., 82 J. Am. Chem. Soc. 1166 (1960).
Skelaxin® monograph, 2001 Physicians' Desk Reference.

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