Pharmacokinetics of epigallocatechin-3-gallate (EGCG) and its interaction with irinotecan in rats

• Main Authors: Meng-Nan Wang, 王孟南
• Other Authors: Tung-Hu Tsai
• Format: Others
• Language: zh-TW
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/64797141373879706346

碩士 === 國立陽明大學 === 傳統醫藥學研究所 === 95 === Abstract Epigallocatechin-3-gallate (EGCG) is the major catechin component of green tea which plays a very important bioactivity. The potential health benefits ascribed to green tea and EGCG include antioxidative effects, cancer chemoprevention, improving cardiovascular health, enhancing weight loss, protecting the skin from the damage caused by ionizing radiation, and others. EGCG has attracted attention through studies of its numerous pharmacological effects and it is therefore very important to obtain accurate pharmacokinetic information. The objective of the present study is to gain an understanding about the pharmacokinetic properties and bioavailability of EGCG in rats. EGCG may also modulate the ATPase activity of P-glycoprotein (P-gp) and down-regulation of multiple drug resistance-1 (MDR1) gene expression, this thesis also discussed the drug-drug interaction between irinotecan and EGCG. For the route of transdermal absorption, EGCG and tea catechins feasibly enhanced theophylline penetrates skin in the in vitro and in vivo animal study. After administration with drug solution on rat’s skin, the amount of theophylline, epicatechin, catechin in skin when incorporating 3% terpineol in the vehicle was higher than the control (P<0.05) after 6 hours administration. No EGCG molecules permeated across the skin, but EGCG concentration in rats’ skin was higher than other drug. In-vivo skin permeation studies showed that 3% terpineol could effectively promote theophylline, epicatechin, catechin, and EGCG absorption across and/or into the skin. The pharmacokinetic data indicate that the oral bioavailability of EGCG in a conscious and freely moving rat was about 4.95%. The disposition of EGCG in the rat blood was fitted well by the two-compartmental model after drug administration (10 mg/kg, i.v.). EGCG may potentially penetrate through the blood-brain barrier at a lower rate which was measured by the brain regional distribution in the rat brain tissues at 15 min after EGCG administration (50 mg/kg, i.v.). The protein binding of EGCG in rat plasma was about 92.4±2.5%. Therefore, drug-drug interaction of EGCG has to take into account in the clinical applications. According to the results of the drug-drug interaction with EGCG and irinotecan, EGCG coadministration could potentially increase the irinotecan concentration by decreasing the intestinal toxicity associated with prolonged dosing.