Pharmacokinetics of TJ-8117(Onpi-to), a drug for renal failure (I): Plasma concentration, distribution and excretion of [3H]-(−)epicatechin 3-O-gallate in rats and dogs

Abstract

TJ-8117 (Onpi-to) is an herbal medicine extracted from a mixture of five crude medicinals (Rhei Rhizoma, Glycyrrhizae Radix, Ginseng Radix, Zingiberis Rhizoma and Aconiti Tuber), which has been developed as a drug for chronic renal failure. (-)Epicatechin 3-O-gallate (ECG), one of the active components of TJ-8117, was labeled with tritium and added to TJ-8117. Pharmacokinetics in plasma, tissue distribution and excretion of radioactivity were investigated following a single oral administration of TJ-8117 containing [3H]ECG ([3H]TJ-8117) in rats and dogs. 1. Following oral administration of [3H]TJ-8117, radioactivity exhibited linear pharmacokinetics in Cmax. Linearity of AUC(0-72 h) was lost at the highest dose of [3H]TJ-8117. Cmax and AUC(0-72 h) were higher in female rats than in male rats, a finding which suggested a sex difference in rats. Plasma levels of radioactivity displayed curves with one peak in dogs, which suggested a species difference between rats and dogs. 2. No accumulation was observed in any tissues in male rats. 3. Within 168 h after administration of [3H]TJ-8117 to male rats, 18.7%, 84.1% and 0.9% of the dose was excreted in urine, feces and expired air, respectively. Data from bile-duct cannulated rats indicated that at least 18.4% of the dose was absorbed.

Pharmacokinetics and pharmacodynamics of a new reformulated microemulsion and the long‐chain triglyceride emulsion of propofol in beagle dogs

“…, 2008). Although dose range is an important factor for dose proportionality (Takizawa et al. , 2004), hepatic blood flow may have a direct influence on this for drugs such as propofol.…”

“…Dose proportionality is a desirable property as it makes predicting the effects of dose adjustments easier (Hummel et al, 2008). It may be mainly affected by dose range, but not by species or size (Takizawa et al, 2004). In our previous study, reformulated microemulsion propofol showed nonlinear pharmacokinetics over the dose range of 0.5-1.5 mg·kg -1 ·min -1 in rats (Lee et al, 2008).…”

“…, 2008). It may be mainly affected by dose range, but not by species or size (Takizawa et al. , 2004).…”

(Bio)chemical Labelling Tools for Studying Absorption & Metabolism of Dietary Phenols - An Overview

“…Using tritiated reducing agents (NaBT 4 and T-L-Selectride ® ), (+)-[3-3 H]-catechin and (-)-[3-3 H]-epicatechin were obtained with specific activities of 5 mCi.g -1 and 7.5 mCi.g -1 respectively. Takizawa et al [29] briefly described the synthetic route to (-)-[3-3 H]-epicatechin-3-O-gallate ((-)-[3-3 H]ECG) via the reduction of the protected ketone 1 (prepared according to Déprez et al [21]). The 4-bromo derivative 7 was first treated overnight with NaBT 4 , followed by additional NaBH 4 for 3 h. This process contributed to reducing the usage of NaBT 4 markedly.…”

“…Synthesis of (-)-4-tritio-epigallocatechin-3-O-gallate ((-)-[4-3 H]EGCG) was reported by Kohri et al using a modification of the procedure developed for the preparation of the 4-deuterio analogue (see Scheme 3) [27]. Esterification with 3,4,5tris(benzyloxy)benzoyl chloride followed by deprotection (H 2 , Pd/C) finally afforded (-)-[3-3 H]ECG (Scheme 5) [29]. The synthetic (-)-[4-3 H]EGCG showed 99.5% radiochemical purity and a specific activity of 13 Ci/mmol.…”