Pharmacokinetics of 6-Gingerol, 8-Gingerol, 10-Gingerol, and 6-Shogaol and Conjugate Metabolites in Healthy Human Subjects

• Published in: Cancer epidemiology, biomarkers & prevention Vol. 17; no. 8; pp. 1930 - 1936
• Main Authors: ZICK, Suzanna M, DJURIC, Zora, RUFFIN, Mack T, LITZINGER, Amie J, NORMOLLE, Daniel P, ALRAWI, Sara, FENG, Meihua Rose, BRENNER, Dean E
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.08.2008
• Subjects: Adult; Area Under Curve; Biological and medical sciences; Catechols - administration & dosage; Catechols - metabolism; Catechols - pharmacokinetics; Chemoprevention; Clinical trial; Fatty Alcohols - administration & dosage; Fatty Alcohols - metabolism; Fatty Alcohols - pharmacokinetics; Female; Ginger; Gingerols; Humans; Male; Medical sciences; Metabolism; Middle Aged; Pharmacokinetics; Shogaol; Tumors; Human; Cancerology; Healthy subject; Conjugated compound; Pharmacokinetics; Metabolite
• ISSN: 1055-9965; 1538-7755
• DOI: 10.1158/1055-9965.EPI-07-2934

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 μg/mL; and 65.6.33 ± 44.4, 18.1 ± 20.3, 50.1 ± 49.3, and 10.9 ± 13.0 μg·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. Conclusion: Six-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol are absorbed after p.o. dosing and can be detected as glucuronide and sulfate conjugates. (Cancer Epidemiol Biomarkers Prev 2008;17(8):1930–6)