Effects of Sho-saiko-to on the Pharmacokinetics and Pharmacodynamics of Tolbutamide in Rats

Nishimura, Nobuhiro; Naora, Kohji; Hirano, Hidenari; Iwamoto, Kikuo

doi:10.1111/j.2042-7158.1998.tb06181.x

Cited by 18 publications

(16 citation statements)

References 13 publications

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“…For example, Xiao Chai Hu Tang and Sho-saiko-To decreased the plasma AUC of prednisolone in rats (Homma et al, 1995); whereas Saiboku-To increased it and Sairei-Tohad no effect. Xiao Chai Hu Tang also decreased the plasma concentration of tolbutamide in rats (Nishimura et al, 1998). However, Xiao Chai Hu Tang also inhibited the gastric emptying and raised intragastric pH, which may contribute to the pharmacokinetic alteration of tolbutamide observed in rats (Nishimura et al, 1998;.…”

Section: G Herb-steroid Interactionsmentioning

confidence: 93%

Interactions of Herbs with Cytochrome P450

Zhou

Gao²,

Jiang

et al. 2003

Drug Metabolism Reviews

357

207

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A resurgence in the use of medical herbs in the Western world, and the co-use of modern and traditional therapies is becoming more common. Thus there is the potential for both pharmacokinetic and pharmacodynamic herb-drug interactions. For example, systems such as the cytochrome P450 (CYP) may be particularly vulnerable to modulation by the multiple active constituents of herbs, as it is well known that the CYPs are subject to induction and inhibition by exposure to a wide variety of xenobiotics. Using in vitro, in silico, and in vivo approaches, many herbs and natural compounds isolated from herbs have been identified as substrates, inhibitors, and/or inducers of various CYP enzymes. For example, St. John's wort is a potent inducer of CYP3A4, which is mediated by activating the orphan pregnane X receptor. It also contains ingredients that inhibit CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Many other common medicinal herbs also exhibited inducing or inhibiting effects on the CYP system, with the latter being competitive, noncompetitive, or mechanism-based. It appears that the regulation of CYPs by herbal products is complex, depending on the herb type, their administration dose and route, the target organ and species. Due to the difficulties in identifying the active constituents responsible for the modulation of CYP enzymes, prediction of herb -drug metabolic interactions is difficult. However, herb-CYP interactions may have important clinical and toxicological consequences. For example, induction of CYP3A4 by St. John's wort may partly provide an explanation for the enhanced plasma clearance of a number of drugs, such as cyclosporine and innadivir, which are known substrates of CYP3A4, although other mechanisms including modulation of gastric absorption and drug transporters cannot be ruled out. In contrast, many organosulfur compounds, such as diallyl sulfide from garlic, are potent inhibitors of CYP2E1; this may provide an explanation for garlic's chemoproventive effects, as many mutagens require activation by CYP2E1. Therefore, known or potential herb -CYP interactions exist, and further studies on their clinical and toxicological roles are warranted. Given that increasing numbers of people are exposed to a number of herbal preparations that contain many constituents with potential of CYP modulation, high-throughput screening assays should be developed to explore herb-CYP interactions.Key Words: Herb; Cytochrome P450; Drug interactions.Abbreviations: Ah, aryl hydrocarbon; AUC, the area of the plasma concentrationtime curve; B[a]P, benzo[a]pyrene; C max , the maximum plasma concentration; CL int , intrinsic clearance; CYP, cytochrome P450; DAD, diallyl disulfide; DAS, diallyl sulfide; DASO, diallyl sulfoxide; DASO 2 , diallyl sulfone; DPS, dipropyl sulfide; DPDS, dipropyl disulfide; K i , inhibition constant; K m , Michaelis -Menten constant; NADPH, nicotinamide adenine dinucleotide phosphate; NNK, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone; N-PiP, N-nitrosopiperidine; PgP, P-glycoprotein; PhIP...

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Section: G Herb-steroid Interactionsmentioning

confidence: 93%

Interactions of Herbs with Cytochrome P450

Zhou

Gao²,

Jiang

et al. 2003

Drug Metabolism Reviews

357

207

View full text Add to dashboard Cite

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“…We have reported that Shosaiko-to elevated plasma concentrations of tolbutamide up to 1 h after oral co-administration. 18,28) In the present studies, plasma tolbutamide concentration tended to be decreased by pre-treatment of Shosaiko-to up to 40 min after dosing. Thus, the present results were not consistent with our previousˆndings.…”

Section: Discussionmentioning

confidence: 64%

Effects of Sho-saiko-to (Xiao Chai Hu Tang), a Chinese Traditional Medicine, on the Gastric Function and Absorption of Tolbutamide in Rats

et al. 2001

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This study was carried out to investigate the eŠects of Sho-saiko-to (Xiao Chai Hu Tang), a Chinese traditional medicine, on the gastric function including the gastric emptying rate (GER) and intragastric pH in rats. Additionally, the eŠects of the GER and intragastric pH on tolbutamide absorption after oral administration were examined. The GER measured at 40 min after dosing was reduced to about 70％ by the pretreatment of Sho-saiko-to (500 mg/kg). The plasma tolbutamide concentration in the rats treated with a 250 mg/kg dose of Sho-saiko-to was signiˆcantly lower than that in the control group. Plasma tolbutamide concentrations increased along with the GER in the group co-administered Sho-saiko-to, and there were signiˆcant correlations between the GERs and plasma levels in both time points at 20 and 40 min after administration. In the study using pylorus-ligated rats, Sho-saiko-to signiˆcantly elevated the intragastric pH, but induced no change in the concentrations of tolbutamide dissolved in the gastric content. Additionally, Sho-saiko-to did not change the area under the plasma concentration-time curve (AUC) of tolbutamide up to 60 min after administration into the stomach loop, and gastric absorption has been considered to minimally contribute to whole absorption of tolbutamide in the gastrointestinal tract. These results indicate that Sho-saiko-to has an inhibitory eŠect on the function of gastric emptying in rats. The reduced gastric emptying could aŠect gastrointestinal absorption, resulting in the lower plasma concentration of tolbutamide after oral administration. Furthermore, it is suggested that Sho-saiko-to can raise the intragastric pH but aŠect neither the intragastric dissolution nor the gastric absorption of tolbutamide.

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“…In contrast, it was also demonstrated that TJ-9 showed an enhancing effect on the initial absorption rate of tolbutamide after oral administration. 12,18) The results of the present studies indicate that the reason for the accelerated absorption of tolbutamide from the gastrointestinal tract does not lie in the dissolution process of this drug. It might be induced by other factors, such as a change in drug transport through the intestinal membrane.…”

Section: Discussionmentioning

confidence: 66%

“…12) Briefly, filtered dissolution medium (50 ml) was added to 100 ml of the internal standard solution (50 mg/ml of chlorpropamide) and 350 ml of an acetonitrile-water mixture (1 : 1), and then shaken for 1 min. After centrifugation at 10000 rpm for 5 min, 10 ml of the supernatant was injected into the chromatograph.…”

Section: Methodsmentioning

confidence: 99%

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

Nishimura

Naora

Hirano

et al. 2001

Biological & Pharmaceutical Bulletin

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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...

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Effects of Sho-saiko-to on the Pharmacokinetics and Pharmacodynamics of Tolbutamide in Rats

Cited by 18 publications

References 13 publications

Interactions of Herbs with Cytochrome P450

Interactions of Herbs with Cytochrome P450

Effects of Sho-saiko-to (Xiao Chai Hu Tang), a Chinese Traditional Medicine, on the Gastric Function and Absorption of Tolbutamide in Rats

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

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