TY - JOUR
T1 - Human pharmacokinetic study of tutin in honey
T2 - A plant-derived neurotoxin
AU - Fields, Barry
AU - Reeve, John
AU - Bartholomaeus, Andrew
AU - Mueller, Utz
N1 - Funding Information:
This work was funded by the New Zealand Ministry for Primary Industries . We thank Lesley Larsen, Janine Cooney, Nigel Joyce and Nigel Perry for the glycoconjugate analyses; AsureQuality staff for the honey and serum analyses, and the Christchurch Clinical Studies Trust staff who conducted the PK study. We also thank Nick Buckley, Chris Schyvens, and Leigh Henderson for helpful discussions.
PY - 2014/10
Y1 - 2014/10
N2 - 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.
AB - 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.
KW - Coriaria arborea
KW - Glycosides
KW - Honey
KW - Neurotoxin
KW - Pharmacokinetics
KW - Tutin
UR - http://www.scopus.com/inward/record.url?scp=84907302598&partnerID=8YFLogxK
UR - http://www.mendeley.com/research/human-pharmacokinetic-study-tutin-honey-plantderived-neurotoxin
U2 - 10.1016/j.fct.2014.07.032
DO - 10.1016/j.fct.2014.07.032
M3 - Article
SN - 0278-6915
VL - 72
SP - 234
EP - 241
JO - Food and Chemical Toxicology
JF - Food and Chemical Toxicology
ER -