Pharmacokinetics of 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol and conjugate metabolites in healthy human subjects.
BACKGROUND
Ginger shows promising anticancer properties. No research has examined the pharmacokinetics of the ginger constituents 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol in humans. We conducted a clinical trial with 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol, examining the pharmacokinetics and tolerability of these analytes and their conjugate metabolites.


METHODS
Human volunteers were given ginger at doses from 100 mg to 2.0 g (N = 27), and blood samples were obtained at 15 minutes to 72 hours after a single p.o. dose. The participants were allocated in a dose-escalation manner starting with 100 mg. There was a total of three participants at each dose except for 1.0 g (N = 6) and 2.0 g (N = 9).


RESULTS
No participant had detectable free 6-gingerol, 8-gingerol, 10-gingerol, or 6-shogaol, but 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol glucuronides were detected. The 6-gingerol sulfate conjugate was detected above the 1.0-g dose, but there were no detectable 10-gingerol or 6-shogaol sulfates except for one participant with detectable 8-gingerol sulfate. The C(max) and area under the curve values (mean +/- SE) estimated for the 2.0-g dose are 0.85 +/- 0.43, 0.23 +/- 0.16, 0.53 +/- 0.40, and 0.15 +/- 0.12 microg/mL; and 65.6.33 +/- 44.4, 18.1 +/- 20.3, 50.1 +/- 49.3, and 10.9 +/- 13.0 microg x hr/mL for 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol. The corresponding t(max) values are 65.6 +/- 44.4, 73.1 +/- 29.4, 75.0 +/- 27.8, and 65.6 +/- 22.6 minutes, and the analytes had elimination half-lives <2 hours. The 8-gingerol, 10-gingerol, and 6-shogaol conjugates were present as either glucuronide or sulfate conjugates, not as mixed conjugates, although 6-gingerol and 10-gingerol were an exception.


CONCLUSIONS
Six-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol are absorbed after p.o. dosing and can be detected as glucuronide and sulfate conjugates.
Zick
Suzanna M
SM
Deoartment of Family Medicine, University of Michigan Medical School, Ann Arbor, MI 48104, USA. szick@med.umich.edu
Djuric
Zora
Z
Ruffin
Mack T
MT
Litzinger
Amie J
AJ
Normolle
Daniel P
DP
Alrawi
Sara
S
Feng
Meihua Rose
MR
Brenner
Dean E
DE
D000328:Adult; D019540:Area Under Curve; D002396:Catechols / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D005233:Fatty Alcohols / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
D002396:Catechols; D005233:Fatty Alcohols; C040115:shogaol; C007845:gingerol