Assessment of cytochrome P450 2D6 in dextromethorphan-herb interactions

Dextromethorphan (DM) is not only an antitussive drug, but also has found other uses in medicine, ranging from pain relief to psychological applications. In recent years, the consumption of herbal medicines has been on the rise all over the world. Although the general public believes herbs are safe health supplements, there are still significant interactions between herbs with DM, which can lead to excessive accumulation and prolonged effects of DM. Human cytochrome P450 2D6 (CYP2D6) is involved in the biotransformation of almost 25% of drugs on the market, although it is expressed at a low level in liver accounting for about 2% of total P450. DM is the first-choice substrate for CYP2D6 phenotyping because it is relatively safe and possesses many favorable pharmacokinetic characteristics for a marker substrate. Until now, numerous studies have reported herbal medicines can induce and/or inhibit human CYP2D6 activity. Hence, DM pharmacokinetics may be changed by herbs affecting the activity of CYP2D6 and then the herb-drug interactions may occur between DM and herbal medicines. Therefore, patients taking DM with herbal medicines that interact with CYP2D6 may require proper dosage adjustments upon DM metabolism.