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Examination of the Pharmacokinetics of Active Ingredients of Ginger in Humans

Abstract

Ginger extracts have been studied in various clinical trials for different indications. However, the pharmacokinetics of the ginger active constituents in human biological matrices is not well investigated. This study aims to develop a LC-MS/MS method for simultaneous measurement of 6-, 8-, and 10-gingerols and 6-shogaol and study their pharmacokinetics in human plasma and colon tissues. A sensitive LC-MS/MS method was established and validated with a low limit of quantification of 2–5 ng/mL. The intra- and inter-day accuracy ranged from −7.3% to 10.4% and from −9.4% to 9.8%, respectively. The intra- and inter-day precision ranged from 0.9% to 10.9% and from 2.0% to 12.4%, respectively. The glucuronide and sulfate metabolites of 6-, 8-, and 10-gingerols and 6-shogaol in plasma and colon tissues were quantified after hydrolysis with β-glucuronidase and sulfatase. After oral dosing of 2.0 g ginger extracts in human, free 10-gingerol and 6-shogaol were detected in plasma with peak concentrations (9.5 ± 2.2 and 13.6 ± 6.9 ng/mL, respectively) at 1 h after oral administration, but no free 6-gingerol and 8-gingerol were detected in plasma from 0.25 to 24 h. The peak concentrations of glucuronide metabolites of 6-, 8-, and 10-gingerols and 6-shogaol were 0.47 ± 0.31, 0.17 ± 0.14, 0.37 ± 0.19, and 0.73 ± 0.54 μg/mL at 1 h, respectively. The peak concentrations of the sulfate metabolites of 6-, 8-, and 10-gingerols and 6-shogaol were 0.28 ± 0.15, 0.027 ± 0.018, 0.018 ± 0.006, and 0.047 ± 0.035 μg/mL at 1 h, respectively. Very low concentrations (2–3 ng/mL) of 10-gingerol glucuronide and sulfate were found in colon tissues. Pharmacokinetic analysis showed that half-lives of these four analytes and their metabolites were 1–3 h in human plasma. No accumulation was observed for 6-, 8-, and 10-gingerols and 6-shogaol and their metabolites in both plasma and colon tissues after multiple daily dosing.

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Acknowledgments

This work was partially supported by the National Institutes of Health (RO1 CA120023 and R21 CA143474 to DS); National Cancer Institute (P30 CA48592 and K07 CA102592 to SZ); University of Michigan Clinical Research Center UL1RR024986; University of Michigan Cancer Center Research Grant (Munn); and University of Michigan Cancer Center Core Grant.

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Correspondence to Suzanna Zick or Duxin Sun.

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Yu, Y., Zick, S., Li, X. et al. Examination of the Pharmacokinetics of Active Ingredients of Ginger in Humans. AAPS J 13, 417–426 (2011). https://doi.org/10.1208/s12248-011-9286-5

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  • DOI: https://doi.org/10.1208/s12248-011-9286-5

Key words

  • 6-Gingerol
  • 8-Gingerol
  • 10-Gingerol and 6-shogaol
  • LC-MS/MS
  • glucuronide
  • sulfate
  • pharmacokinetics