Pharmacokinetics of (-)-Epicatechin-3-O-gallate, an Active Component of Onpi-to, in Rats

Abstract

(-)-Epicatechin-3-O-gallate (ECG), a component of Rhei Rhizoma, is one of the active components of Onpi-to, a herbal medicine composed of five crude drugs (Rhei Rhizome, Glycyrrhizae Radix, Ginseng Radix, Zingiberis Rhizoma and Aconiti Tuber), which has been used in patients with chronic renal failure. Pharmacokinetics of ECG was investigated in male rats employing an HPLC-electrochemical detection method. 1. Following oral administration of ECG, ECG plasma levels revealed curves characterized by peaks at 0.065, 0.063 and 0.085 h corresponding to dosages of 12.5, 25.0 and 50.0 mg/kg at mean concentrations of 49.62, 212.89 and 464.04 ng/ml, respectively. Plasma levels subsequently declined bi-exponentially. ECG demonstrated nonlinear pharmacokinetics in terms of C(max) and AUC(0-inf). 2. The absolute bioavailability values (F) were 1.02, 1.47 and 3.30% at doses of 12.5, 25.0, and 50.0 mg/kg, respectively. 3. Following intravenous injection of ECG, plasma levels of ECG decreased with the gamma-elimination half-life (t(1/2gamma)) of 4.03 h. 4. Following oral administration of ECG, urinary levels of ECG were lower than the quantitation limit. Moreover, cumulative excretion of the metabolites, delta-(3,4-dihydroxyphenyl)-gamma-valerolactone and delta-(3-methoxy-4-hydroxyphenyl)-gamma-valerolactone, was 2.45 and 0.23% of dose, respectively, up to 30 h after dosing.

The Potential of Flavonoids to Influence Drug Metabolism and Pharmacokinetics by Local Gastrointestinal Mechanisms

“…A rather low oral bioavailability was also shown for another flavanol in rats, namely epicatechin-3-gallate (ECG). After gastric intubation of ECG at a concentration of 113 µmol/kg BW, absolute bioavailability was 3.3% [49].…”

Pharmacokinetics of Green Tea Catechins in Maternal and Fetal Body Compartments

“…Although the absolute concentrations of individual catechins detected in fetal organs are low, they are higher than those reported in adult rats (Meng et al, Takizawa et al (2003) reported that trace amounts of catechins were found in the liver and kidney when tea extract was given for three days. Tmax of the first dominant catechin peaks is around one hour.…”

“…Many catechin pharmacokinetic studies have been reported in non-pregnant adult rats with wide ranges of EGCG doses (Chen et al, 1997;Nakagawa and Miyazawa, 1997;Kim et al, 2000;Chow et al, 2001;Natsume et al, 2003;Takizawa et al, 2003). Chow's and Takizawa's studies observed non-linear and two-compartmental phenomena in catechin kinetics.…”

Analysis Methods and Recent Advances in Nonlinear Pharmacokinetics from In Vitro through In Loci to In Vivo

“…56) The authors concluded that this nonlinear absorption is attributed to saturation of theˆrst-pass eŠect in the intestinal micro‰ora or the liver, which can be simply determined by an in loci experiment. Oral absorption models which are timedependent have been proposed to explain irregular absorption proˆles from the intestine.…”