Changes in the Dissolution of Tolbutamide by a Traditional Chinese Medicine, Sho-saiko-to (Xiao Chaihu Tang).

Abstract

Tolbutamide is classified into sulfonylureas prescribed for the treatment of diabetic patients. The sulfonylureas have a potent hypoglycemic effect and sometimes show delayed and erratic absorption, leading to unexpected hypoglycemia. [1][2][3] Simons et al. reported that absorption patterns of tolbutamide were well correlated to the dissolution rate from the tablet. 4) Although the rate of drug absorption is often not important in chronic therapy, some studies have suggested that the absorption kinetics of tolbutamide may determine its hypoglycemic efficacy. Kivistö and Neuvonen demonstrated an increased absorption of tolbutamide with an enhancement of blood glucose-lowering effects, presumably due to the improved dissolution of this sulfonylurea by the increase in gastric pH. 5) Additionally, it was reported that an increase in the in vitro dissolution rate of tolbutamide tablets induced an increase in absorption rates of tolbutamide and a decline in blood sugar levels in the early period after drug administration.6) Thus, the dissolution rate is considered an important factor affecting absorption and efficacy after the oral administration of tolbutamide.As the therapeutic use of traditional Chinese medicines combined with other synthetic or biotechnological drugs has been increasing in Japan, serious adverse effects or drug interactions caused by them have recently been reported. [7][8][9] Sho-saiko-to (TJ-9; Xiao Chaihu Tang) is a major traditional Chinese medicine consisting of seven herbals, a mixture of several crude drugs containing many natural substances. Since in many cases traditional Chinese medicines are taken with other drugs, it is likely that the dissolution and absorption of concomitant drugs in the gastrointestinal tract is influenced by the presence of traditional Chinese medicines.In this study, we employed TJ-9 as a traditional Chinese medicine, since TJ-9 is one of the most commonly prescribed preparations. The effects of TJ-9 and its constituents on the in vitro dissolution of tolbutamide were examined. MATERIALS AND METHODS MaterialsThe reagent of tolbutamide was obtained from Sigma Chemical Co. (St. Louis, MO, U.S.A.). Tolbutamide tablets (Rastinon ® ) and five traditional Chinese preparations, Kakkon-to (TJ-1), Hachimi-jio-gan (TJ-7), Shosaiko-to (TJ-9), Chorei-to (TJ-40), Shakuyaku-kanzo-to (TJ-68), were purchased from Aventis Pharma, Ltd. (Tokyo, Japan) and Tsumura & Co., Ltd. (Tokyo, Japan), respectively. The TJ-9 extract, which was an extract from the mixture of herbal medicines composing TJ-9, and Glycyrrhizae Radix (GR) extract, which includes Glycyrrhizic acid (glycyrrhizin, GL), were kindly gifted from Tsumura & Co., Ltd. The content of GL in GR was 12.4% (determined by Tsumura & Co., Ltd.). The traditional Chinese preparations of TJ-1, TJ-7, TJ-9, TJ-40 and TJ-68 were oral dosage preparations which included additives prescribed for therapeutic use. Herbal compositions of these five preparations are summarized in Table 1. GL was obtained from Tokyo Kasei Kogyo Co., Ltd. (Tokyo...

Transepithelial Permeation of Tolbutamide across the Human Intestinal Cell Line, Caco-2

“…16) Quantiˆcation of benzoic acid was also performed by the reported HPLC method. 17) Data analysis: Permeation rates of tolbutamide were calculated using the permeated amount of the drug a n da r ee x p r e s s e da sn m o l W min W cm 2 .…”

Hepatoprotective and Anti-fibrotic Agents: It's Time to Take the Next Step

“…The mixture that is also known as TJ-7 or Xiao Chaihu Tang is composed of seven herbals (Figure 9 ). It contains 17.5% root of Bupleurum falcatum (Bupleurum, Chai Hu, Saiko), 5.0% root/stolon of Glycyrrhiza uralensis (Licorice, Gan Cao, Kanzou), 7.5% root w/o rootlets of Panax ginseng (Asian ginseng, Ren Shen, Ninjin), 12.5% tuber w/o cork layer of Pinelliae ternatae (Pinellia, Ban Xia, Hange), 7.5% rot w/o periderm of Scutellaria baicalensis (Baical skullcap, Huang Qin, Ougan), 2.5% root/rhizome of Zingiber officinale (Ginger, Sheng Jiang, Shokyo), 7.5% fruit of Ziziphus jujube (Jujube, Da Zao, Daiso), and 40% additives (Nishimura et al, 2001 ; Wen, 2007 ). Each of these herbs contains several active biochemical constituents that are considered to predict their pharmacological effects.…”

Change in tolbutamide permeability in rat jejunum and Caco-2 cells by Sho-saiko-to (Xiao Chai Hu Tang), a Chinese traditional medicine

“…Therefore, to predict and prevent serious reactions induced by drug interaction, it is necessary to characterize the mechanism for increased absorption of tolbutamide after co‐administration with Sho‐saiko‐to. In previous studies, we have shown that Sho‐saiko‐to did not affect the gastric absorption of tolbutamide in rats [11] and that dissolution of tolbutamide was not changed by Sho‐saiko‐to [12] . Thus, we focused on the absorption processes of the drug in the small intestine.…”