Effects of Sairei‐to on the pharmacokinetics of nifedipine in rats

Ikehata, Mika; Ohnishi, Noriaki; Matsumoto, Tsuyoshi; Kiyohara, Yoshifumi; Maeda, Atsushi; Kawakita, Tetsuya; Takara, Kohji; Yokoyama, Teruyoshi

doi:10.1002/ptr.2234

Cited by 6 publications

(3 citation statements)

References 19 publications

(19 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, a discrepant report in terms of Saireito (Kanebo Ltd.) on the pharmacokinetic of nifedipine in vivo has been published by Ikehata et al [17]. Although the values of C max and AUC for the control groups were higher than those reported by Ikehata, the values of F were almost the same.…”

Section: Discussionmentioning

confidence: 87%

Experimental Adjustment on Drug Interactions through Intestinal CYP3A Activity in Rat: Impacts of Kampo Medicines Repeat Administered

Kinoshita

Yamaguchi

Hou

et al. 2011

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

To provide the information that is necessary for making the proper use of kampo medicines, we have proposed the adequate methodology focused on the following issues: (i) kampo medicines emphasize the effects produced by the combination of herbal drugs rather than the individual effect of any single herb and (ii) Intestinal CYP3A has become a key factor for the bioavailability of orally administrated drugs. In the present study, we investigated both the in vivo and in vitro effects of Saireito and Hochuekkito (kampo formulas) on CYP3A activities. From our study, oral pre-treatment with Saireito or Hochuekkito did not affect the pharmacokinetics of nifedipine after intravenous administration to rats. When nifedipine was administered to rat intrajejunum, a significant decrease of AUC was showed by pre-treatment with both kampo formulas. Saireito pre-treatment led to 80% decrease in C max of nifedipine. Saireito caused significant increases in both protein expression and metabolic activity of CYP3A in intestinal microsome, whereas it had no effect on CYP3A in hepatic microsome. Our result also showed that this affect of Saireito can be gone by wash-out with 1 week. These findings demonstrated that Saireito may induce CYP3A activity of intestine but not of liver in rats. When resources for research are limited, well-designed scientific studies except clinical trials also have many advantages.

show abstract

Section: Discussionmentioning

confidence: 87%

Experimental Adjustment on Drug Interactions through Intestinal CYP3A Activity in Rat: Impacts of Kampo Medicines Repeat Administered

Kinoshita

Yamaguchi

Hou

et al. 2011

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

show abstract

“…The high bioavailability is probably due to the avoidance of hepatic first-pass elimination 18) by CA absorbed from the rectum, and the lower contribution of metabolic enzymes and transporters in the intestine to the absorption of CA from the rectum. Further investigations are needed to clarify the absorption mechanism of CA upon rectal administration of goreisan suppository because intestinal absorption of CA in rats is reported to be affected by the metabolic enzyme CYP 3A4 19) and the transporter gp-1. 20) This result suggested that CA in goreisan suppository was rapidly absorbed rectally, implying the rapid onset of a medical effect.…”

Section: Discussionmentioning

confidence: 99%

Preparation of Goreisan Suppository and Pharmacokinetics of <i>trans</i>-Cinnamic Acid after Administration to Rabbits

Katagiri

Miyazaki

Uchino

et al. 2014

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Goreisan suppository is prepared as a hospital preparation, and successfully used for the treatment of diarrhea and vomiting in young children with common cold. While clinical efficacy of the suppository has been reported, few studies have been carried out to clarify the preparation procedure and pharmacokinetics of the suppository. In this study, trans-cinnamic acid (CA) was used as a representative substance of goreisan constituents, and assayed by HPLC-UV. We investigated the properties of goreisan suppositories prepared using various sizes of pulverized goreisan extract granules, in vitro dissolution profiles using the reciprocating dialysis tube method, and pharmacokinetics in rabbits compared with those for goreisan enema. Mass and content uniformity tests on the suppositories of three size fractions, 0-75, 75-150, and 150-300 µm, showed good acceptance for all kinds of suppository. Storage stability at 4°C was maintained until 4 months. In vitro dissolution of CA from the suppository was proportional to time until 45 min, and slower than that from the enema. Finally, 80% of CA had dissolved at 60 min. Pharmacokinetic study in rabbits revealed that the area under the plasma concentration-time curve from 0 to 120 min (AUC 0-120 min ) of the suppository was twice that of the enema. Moreover, from a study in rabbits using CA injection and CA suppository, we revealed that CA was rapidly and well absorbed from the rectum, showing 84% absolute bioavailability. Thus, we illustrated the defined preparation procedure of the suppository and the superiority of the suppository over the enema. This study will support evidence that the suppository is fast-acting and efficacious in clinical use.

show abstract

“…Because Kampo medicines include many kinds of herbs, Kampo-western drug interaction mediated by this enzyme was anticipated. In fact, among a number of Kampo medicines the high dose of saireito was suggested to have the ability to enhance and inhibit the metabolism of nifedipine in rats (8); meanwhile, rikkunshito, yokukansan, and boiogito have minimal effect on the metabolism of triazolam in mice (9). However, these kinds of investigations are quite limited and there is no information concerning CYP3A-mediated drug interaction for most of the Kampo medicines, even for those that are used frequently.…”

Section: Introductionmentioning

confidence: 99%

In Vivo Inhibition of CYP3A-Mediated Midazolam Metabolism by Anchusan in Rats

et al. 2011

View full text Add to dashboard Cite

Abstract. Cytochrome P450 (CYP)-mediated drug interactions caused by Kampo medicine have not been investigated sufficiently. The current study was conducted to reveal the effect of anchusan, a commonly used Kampo formula for gastrointestinal disease, on CYP3A-mediated drug metabolism in rats. The pharmacokinetics of midazolam (MDZ) was investigated after the single or one-week administration of anchusan (500 mg/kg) to evaluate its inhibitory and inducible effect on CYP3A, respectively. MDZ was administrated 16 h after the last anchsan treatment in the multiple dose study, while their intervals were 2 or 16 h in the single dose study. Unexpectedly, the multiple-pretreatment of anchusan increased the AUC of MDZ by 2.4-fold rather than decreasing it, and the CYP3A contents and activities were unchanged in hepatic and intestinal microsomes of these rats. In contrast, no significant inhibitory effects on MDZ metabolism were observed by the single anchusan pretreatment. In vitro study showed that the preincubation of anchusan and some of its component extracts with rat liver microsomes reduced CYP3A activity in a time-and NADPH-dependent manner. These results suggested that anchusan increased the serum MDZ concentration in rats, at least in part, by the time-dependent inhibition of CYP3A.

show abstract

Effects of Sairei‐to on the pharmacokinetics of nifedipine in rats

Cited by 6 publications

References 19 publications

Experimental Adjustment on Drug Interactions through Intestinal CYP3A Activity in Rat: Impacts of Kampo Medicines Repeat Administered

Experimental Adjustment on Drug Interactions through Intestinal CYP3A Activity in Rat: Impacts of Kampo Medicines Repeat Administered

Preparation of Goreisan Suppository and Pharmacokinetics of <i>trans</i>-Cinnamic Acid after Administration to Rabbits

In Vivo Inhibition of CYP3A-Mediated Midazolam Metabolism by Anchusan in Rats

Contact Info

Product

Resources

About