Dextromethorphan transdermal delivery device

A method of treating a neurological disorder in a subject in need thereof, the method comprising applying a transdermal delivery device to the skin of the subject once daily, wherein the transdermal delivery device comprises an adhesive layer comprising an adhesive in the amount of about 65% to about 85%, dextromethorphan in an amount of about 2% to about 12%, a permeation enhancer in an amount of about 6% to about 12%, and optional other ingredients in an amount of about 0% to about 20%, wherein the transdermal delivery device is configured to provide dextromethorphan about 15 mg/day to about 40 mg/day to the subject, wherein the subject is not co-administered a CYP2D6 inhibitor, and

• wherein the neurological disorder is depression, stroke, traumatic brain injury, seizure, methotrexate neurotoxicity, Parkinson's disease, autism, Alzheimer's disease, or a combination thereof,
• wherein the permeation enhancer is isopropyl myristate, wherein dextromethorphan is the only active agent in the transdermal delivery device, and wherein the subject does not suffer from a cough and/or does not need an antitussive,
• wherein the subject is a human subject and the applying results in one or more of the following pharmacokinetic profile in the human subject:
• a. a mean Cmax of dextromethorphan of about 3 ng/ml to about 12 ng/ml at day 1 post application;
• b. a mean AUC0-24 of dextromethorphan of about 40 ng*h/ml to about 150 ng*h/ml at day 1 post application;
• c. a mean ratio of C24h/C12h of dextromethorphan of about 1 to about 1.5 at day 1 post application;
• d. a mean ratio of C24h/C6h of dextromethorphan of about 1.5 to about 2.5 at day 1 post application;
• e. a mean ratio of C24h/C18h of dextromethorphan of about 0.85 to about 1.3 at day 1 post application;
• f. a mean Cmax of dextrorphan of not more than 2 ng/ml at day 1 post application;
• g. a mean AUC0-24 of dextrorphan of not more than 10 ng*h/ml at day 1 post application;
• h. a mean ratio of Cmax of dextromethorphan to Cmax of dextrophan of at least about 5 at day 1 post application;
• and
• i. a mean ratio of AUC0-24 of dextromethorphan to AUC0-24 of dextrophan of at least about 5 at day 1 post application.