Over the last 150 years a number of people in New Zealand
have been incapacitated, hospitalised, or died from eating honey contaminated
with tutin, a plant-derived neurotoxin. A feature of the most recent poisoning
incident in 2008 was the large variability in the onset time of clinical signs
and symptoms of toxicity (0.5 to 17 h). To investigate the basis of this
variability a pharmacokinetic study was undertaken in which 6 healthy males
received a single oral dose of tutin-containing honey giving a tutin dose of
1.8μg/kg body weight. The serum concentration-time curve for all volunteers
exhibited two discrete peaks with the second and higher level occurring at
approximately 15 hours post-dose. Two subjects reported mild, transient
headache at a time post-dose corresponding to maximum tutin concentrations.
There were no other signs or symptoms typical of tutin intoxication such as
nausea, vomiting, dizziness or seizures. Pharmacokinetic analysis using a
two-site absorption model resulted in a good fit to the observed concentration
data. A novel analytical method subsequently revealed the presence of glycoside
conjugates of tutin in addition to unconjugated tutin in honey. These
pharmacokinetic data will be important to better define a safe maximum tutin
concentration in honey.
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