An autopsy case of BRON^TM overdose with multiple drug ingestion

A man in his forties was found dead in his friend's home, with moderate putrefaction. Quantitative toxicological analysis showed that concentrations of caffeine, chlorpheniramine, dihydrocodeine, and methylephedrine were 183.3 µg/mL, 0.533 µg/mL, 2.469 µg/mL and 8.336 µg/mL, respectively. Ephedrine, amitriptyline, nortriptyline, etizolam, fluvoxamine and 7-aminoflunitrazepam were detected in an aortic blood sample. Caffeine, chlorpheniramine, dihydrocodeine and methylephedrine are the main components of BRON^TM, an over-the-counter antitussive sold in Japan. Those concentrations in blood were within fatal ranges. Caffeine is classified as a methylxanthine and is mainly metabolized by cytochrome P450 (CYP)1A2. Fluvoxamine is a potent CYP1A2 inhibitor. Blood fluvoxamine concentration was within the therapeutic range, but would have increased blood caffeine level by the inhibition of caffeine metabolism. The conclusion was that his death was caused by BRON^TM overdose. Inhibition of caffeine metabolism may increase blood caffeine concentrations. This suggests that more attention should be paid to potential interactions between multiple drugs.