A Study of the in Vitro Interaction between Caffeine and Dextromethorphan at High Concentrations Using Human Liver Microsomes

Abstract

Dextromethorphan is dextro-rotatory isomer of synthetical opioid levorphanol. In humans, it is mainly demethylated into dextrorphan after ingestation, by cytochrome P450 via CYP2D6 activity. Dextromethorphan is clinically used as a cough suppressant and exhibits it effect by depressing the medullary cough center in the mid brain. In therapeutic dosage, the drug has no effect on euphoria, pain relief, and also other unwanted toxicities. Unfortunately, dextromethorphan is presently used as an illicit party drug because of its euphoric effect. Dextromethorphan, when used at a dosage over 360 mg in combination with other creative drugs such as Kratom and other sedative drugs, causes the experiences of euphoria and pain relief. The number of abusers has reportedly been increasing in Thailand, and also has been related to several intoxicated deaths. In Thailand, dextromethorphan has been popularly used in a combination with caffeine because caffeine is normally a component in refreshments. In this study, Dextromethorphan and its main metabolite (dextrorphan) were extracted via in vitro reactions by mixed-mode (cation-exchange and reversed-phase) solid phase extraction and measured by gas chromatography and mass spectrometer.

In vitro interaction between dextromethorphan and caffeine was analysed to define its relationship. Metabolization of dextromethorphan (0.1 - 5.0 ug/ml) was significantly inhibited (P < 0.001)  by caffeine (10-100 ug/ml) but not for its main metabolite, dextrophan. These results suggest that toxicology of the coexistence of dextromethorphan  and a high concentration of caffeine presence produces longer and stronger effects in the human body because the unchanged form of dextromethorphan  remains long term while there is a high level of caffeine