TY - JOUR
T1 - Absorption of dimethoxycinnamic acid derivatives in vitro and pharmacokinetic profile in human plasma following coffee consumption
AU - Farrell, Tracy L.
AU - Gomez-Juaristi, Miren
AU - Poquet, Laure
AU - Redeuil, Karine
AU - Nagy, Kornél
AU - Renouf, Mathieu
AU - Williamson, Gary
PY - 2012/9/1
Y1 - 2012/9/1
N2 - Scope: This study reports the 24 h human plasma pharmacokinetics of 3,4-dimethoxycinnamic acid (dimethoxycinnamic acid) after consumption of coffee, and the membrane transport characteristics of certain dimethoxycinnamic acid derivatives, as present in coffee. Methods and results: Eight healthy human volunteers consumed a low-polyphenol diet for 24 h before drinking 400 mL of commercially available coffee. Plasma samples were collected over 24 h and analyzed by HPLC-MS2. Investigation of the mechanism of absorption and metabolism was performed using an intestinal Caco-2 cell model. For the first time, we show that dimethoxycinnamic acid appears in plasma as the free aglycone. The time to reach the Cmax value of approximately 0.5 μM was rapid, Tmax = 30 min, and showed an additional peak at 2-4 h for several subjects. In contrast, smaller amounts of dimethoxy-dihydrocinnamic acid (Cmax ∼ 0.1 μM) peaked between 8 and 12 h after coffee intake. In the cell model, dimethoxycinnamic acid was preferentially transported in the free form by passive diffusion, and a small amount of dimethoxycinnamoylquinic acid hydrolysis was observed. Conclusion: These findings show that dimethoxycinnamic acid, previously identified in plasma after coffee consumption, was rapidly absorbed in the free form most likely by passive diffusion in the upper gastrointestinal tract.
AB - Scope: This study reports the 24 h human plasma pharmacokinetics of 3,4-dimethoxycinnamic acid (dimethoxycinnamic acid) after consumption of coffee, and the membrane transport characteristics of certain dimethoxycinnamic acid derivatives, as present in coffee. Methods and results: Eight healthy human volunteers consumed a low-polyphenol diet for 24 h before drinking 400 mL of commercially available coffee. Plasma samples were collected over 24 h and analyzed by HPLC-MS2. Investigation of the mechanism of absorption and metabolism was performed using an intestinal Caco-2 cell model. For the first time, we show that dimethoxycinnamic acid appears in plasma as the free aglycone. The time to reach the Cmax value of approximately 0.5 μM was rapid, Tmax = 30 min, and showed an additional peak at 2-4 h for several subjects. In contrast, smaller amounts of dimethoxy-dihydrocinnamic acid (Cmax ∼ 0.1 μM) peaked between 8 and 12 h after coffee intake. In the cell model, dimethoxycinnamic acid was preferentially transported in the free form by passive diffusion, and a small amount of dimethoxycinnamoylquinic acid hydrolysis was observed. Conclusion: These findings show that dimethoxycinnamic acid, previously identified in plasma after coffee consumption, was rapidly absorbed in the free form most likely by passive diffusion in the upper gastrointestinal tract.
KW - Bioavailability
KW - Caco-2 cells
KW - Coffee
KW - Human plasma
KW - Phenolic acids
UR - http://www.scopus.com/inward/record.url?scp=84865726906&partnerID=8YFLogxK
U2 - 10.1002/mnfr.201200021
DO - 10.1002/mnfr.201200021
M3 - Article
C2 - 22865606
AN - SCOPUS:84865726906
VL - 56
SP - 1413
EP - 1423
JO - Molecular Nutrition & Food Research
JF - Molecular Nutrition & Food Research
SN - 1613-4125
IS - 9
ER -