Poisoning with tilidine and naloxone: toxicokinetic and clinical observations

The opioid analgesic tilidine and its metabolites were detected by high performance liquid chromatography (HPLC) with UV-detection in serum from a 28 year-old woman who ingested 100 ml Valoron (o)N containing 6.94 g of tilidine and about 0.56 g of naloxone with suicidal intention. Data on the toxicokinetics of tilidine in severe poisonings are missing. Therefore we followed serum concentrations of tilidine and metabolites for 48 or 96 h and for the first time calculated basic kinetic parameters in a massive life threatening poisoning. Serum concentration of tilidine 3 h after ingestion was 38.1 mg/l which is about 70 times of the upper therapeutic level in man and about ninefold above toxic concentrations known so far. The concentration of nortilidine, the primary active metabolite at this time was 18.8 mg/l. The terminal elimination half life's of tilidine and nortilidine were explicit, prolonged with 23.9 and 13.9 h respectively. The competitive opiate antagonist naloxone, which is added as a part of the industrially produced preparation Valoron N solution to minimise oral abuse is not able to prevent ventilatory depression in massive overdoses.