| TECHNOLOGY | The therapeutic utility of drug is leveraged via the elevated blood levels of dextromethorphan. Quinidine sulfate, a well-known, well-established cardiac anti-arrhythmic is used at a low dose to inhibit the cytochrome P450 2D6 enzyme responsible for the (rapid) metabolism of dextromethorphan. The amount of quinidine sulfate present in the product is ten to 20-fold lower than the normal therapeutic daily dose used in the treatment of arrhythmia. Furthermore, the addition of quinidine provides, on average, forty-fold elevated levels of dextromethorphan compared to levels measured following dosing with DM only. Therefore, through the use of an enzyme inhibitor, dextromethorphan may be effective in treating neurologic disorders even at doses as low as those recommended for over-the-counter cough suppression in adults. With regard to chronic cough, medical experts recognize DM as a safe non-narcotic cough suppressant. Dextromethorphan apparently works via several different mechanisms to suppress cough. Dextromethorphan is a centrally acting antitussive that depresses the medullary cough center via sigma-receptor agonism, subsequently interrupting cough impulse transmission. It also decreases cough receptor sensitivity. A drawback in exploring the pharmacological utility of dextromethorphan has been its rapid metabolism, which results in low blood levels of DM regardless of the starting dose, or dose form such as "controlled-release". The metabolite, dextrorphan exhibits pharmacology similar to dextromethorphan, but does not cross the blood-brain barrier as readily as DM. Antitussive agents must cross the blood-brain barrier if they are to exert their centrally active cough suppressing effect. Effective levels of dextromethorphan are therefore critical to the use of DM as an effective non-narcotic alternative for patients with chronic cough. |
|
Want more information ? Interested in the hidden information ? Click here and do your request. |