title: Human pharmacokinetic study of tutin in honey; a plant-derived neurotoxin.
abstract: 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 (0.5-17 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 1.8 μg/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 h 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.
authors.affiliation: Food Standards Australia New Zealand, 55 Blackall St., Barton, ACT 2600, Australia. Electronic address: barry.fields@foodstandards.gov.au.
authors.forename: Barry A
authors.initials: BA
authors.lastname: Fields
authors.affiliation: New Zealand Ministry for Primary Industries, Pastoral House, 25 The Terrace, Wellington, New Zealand.
authors.forename: John
authors.initials: J
authors.lastname: Reeve
authors.affiliation: Therapeutics Research Centre, School of Medicine, University of Queensland, Queensland, Australia; School of Pharmacy, Faculty of Health, University of Canberra, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Bartholomaeus
authors.affiliation: Food Standards Australia New Zealand, 55 Blackall St., Barton, ACT 2600, Australia.
authors.forename: Utz
authors.initials: U
authors.lastname: Mueller
mesh_terms: D000293:Adolescent; D000328:Adult; D004305:Dose-Response Relationship, Drug; D005506:Food Contamination / Q000032:analysis; D064368:Healthy Volunteers; D006722:Honey / Q000032:analysis*; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009498:Neurotoxins / Q000097:blood* / Q000493:pharmacokinetics*; D010852:Picrotoxin / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D012717:Sesquiterpenes / Q000097:blood* / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D009498:Neurotoxins; D010852:Picrotoxin; D012717:Sesquiterpenes; C009614:tutin
keywords: Coriaria arborea; Glycosides; Honey; Neurotoxin; Pharmacokinetics; Tutin