Pharmacokinetic Parameters of the Lappaconitine, Glycyrrhizic Acid and Methyluracil Combination Exhibiting Antiarrhythmic Properties upon Single Intragastric Administration in Various Doses

This study was performed to evaluate and compare the pharmacokinetic parameters between two dosage formulations of hesperidin and naringenin: mixture and tablet. Our objective was to determine that the flavonoid tablet does not significantly modify the pharmacokinetic parameters compared with the mixture. For this study, we administered 161 mg/kg of either mixture (Mix-160) or tablet composed of hesperidin and by intragastric administration. Blood microsamples were collected from tail vein up to 24 h. Serum flavonoid extraction was performed by solid phase extraction and analyzed by LC-MS/MS of triple quadrupole (QqQ). Serum concentration vs. time plot showed that data fitted for a first-order model. The pharmacokinetic parameters were calculated by a noncompartmental model. The results showed that the absorption constant is higher than the elimination constant. The first concentration was found at five minutes, and minimal concentration at 24 h after administration, suggesting a enterohepatic recirculation phenomena and regulation of liver cytochromes’ activity. We did not find meaningful differences between the pharmacokinetic parameters of both samples. We concluded that tablet form did not interfere with the bioavailability of hesperidin and naringenin, and it could be a suitable candidate for developing a drug product.

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Development of an UPLC–MS/MS assay to determine psoralidin in rat plasma and its application in a pharmacokinetic study after intragastric administration

Acta Chromatographica ◽

10.1556/1326.2019.00679 ◽

2020 ◽

Vol 32 (4) ◽

pp. 215-218

Author(s):

Feng Feng ◽

Xiunan Jiang ◽

Jieying Qiu ◽

Hongyu Wu ◽

Xiaojun Cai ◽

...

Keyword(s):

Pharmacokinetic Study ◽

Internal Standard ◽

Apparent Volume ◽

Ultra Performance Liquid Chromatography ◽

Rat Plasma ◽

Volume Of Distribution ◽

Pharmacokinetic Parameters ◽

Intragastric Administration ◽

Rat Tissues ◽

Pharmacokinetic Characteristic

Psoralidin has a variety of pharmacological activities, such as anti-tumor, anti-depressant, and anti-inflammatory activities. This study aims at developing a rapid ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method to determine psoralidin in rat plasma and studying the pharmacokinetic characteristic of psoralidin after intragastric administration of 20 and 40 mg/kg. Alpinetin was used as an internal standard (IS), and the plasma samples were precipitated with acetonitrile. The calibration curves were linear over the range of 0.2–250 ng/mL (R2 = 0.993). The pharmacokinetic parameters were calculated by DAS 3.0. Half-life (t1/2) was 7.2 ± 0.97 h and 7.1 ± 0.27 h for different dosages, respectively. Tmax was 4.2 ± 1.1 h and 4.0 ± 1.1 h for different dosages, respectively. Apparent volume of distribution (Vd) for different dosages was 630.1 ± 168.8 and 600.1 ± 138.8 L/kg, respectively. Clearance (CL) was 105.6 ± 29.2 and 100.6 ± 22.2 L/h/kg for different dosages, indicating that psoralidin was mainly distributed in rat tissues. The pharmacokinetic study provided important information for further clinical application in the treatment of cancer and osteoporosis.

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Pharmacokinetics and Tissue Distribution Study of Modified Xiaochaihu Granules Against Gastric Ulcer Induced by Ethanol in Rats by UPLC-MS/MS

Natural Product Communications ◽

10.1177/1934578x20935216 ◽

2020 ◽

Vol 15 (7) ◽

pp. 1934578X2093521

Author(s):

Xin Chen ◽

Yuan-Chun Ma ◽

Mengling Yang ◽

Pengtao You ◽

Dan Liu ◽

...

Keyword(s):

Gastric Ulcer ◽

Tissue Distribution ◽

Glycyrrhizic Acid ◽

Rat Plasma ◽

Negative Ion ◽

Intragastric Administration ◽

Rat Tissues ◽

Berberine Hydrochloride ◽

Distribution Study ◽

Tissue Distribution Study

Gastric ulcer (GU) is one of the major gastrointestinal disorder diseases, with increasing incidence and prevalence globally. Modified Xiaochaihu granules (MXCHG) have been used effectively for treating chronic gastritis and GU clinically. To investigate the pharmacokinetics and tissue distribution of MXCHG, an ultraperformance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) method was established for the simultaneous determination of 8 bioactive ingredients (baicalin, wogonoside, baicalein, liquiritin, glycyrrhizic acid, berberine hydrochloride, saikosaponin a, and saikosaponin d) in rat plasma and various tissues using puerarin as an internal standard (IS). The biological samples were pretreated by protein precipitation with acetonitrile. The chromatographic separation was carried out on a C18 column with a gradient mobile phase consisting of acetonitrile and 0.1% formic acid in water. All analytes and IS were quantitated through ESI in the positive/negative ion multiple reaction monitoring mode. The mass transitions were as follows: m/z 445.0 → 268.5 for baicalin, m/z 458.7 → 282.8 for wogonoside, m/z 269.2 → 222.6 for baicalein, m/z 417.0 → 254.8 for liquiritin, m/z 822.1 → 350.8 for glycyrrhizic acid, m/ z 336.0 → 319.9 for berberine hydrochloride, m/z 780.3 → 618.5 for saikosaponin, and m/z 415.0 → 294.6 for the IS. The validated method was successfully applied to the pharmacokinetics and tissue distribution study of 8 compounds in rat plasma and tissues after the intragastric administration of MXCHG. The results demonstrated that 8 components were distributed widely and rapidly in various rat tissues after intravenous administration. Tissue deposition of the compounds in the rats was mainly in the small intestine and stomach. The present study can provide more useful information to guide the clinical use of MXCHG and the developed analytical method can also be applied for further clinical pharmacokinetic studies.

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Effects of Acupuncture at St36 on Pharmacokinetics of Schisandra lignans in rats

Acupuncture in Medicine ◽

10.1136/acupmed-2014-010622 ◽

2015 ◽

Vol 33 (3) ◽

pp. 223-229 ◽

Cited By ~ 1

Author(s):

De Ji ◽

Ziwan Ning ◽

Chunqin Mao ◽

Yong Sun ◽

Jing Liu ◽

...

Keyword(s):

Plasma Concentration ◽

Study Groups ◽

Acupuncture Group ◽

Pharmacokinetic Parameters ◽

Intragastric Administration ◽

Schisandrin B ◽

Time Curve ◽

Acupuncture Stimulation ◽

Concentration Time ◽

Plasma Concentration Time Curve

Objective To investigate the influence of acupuncture at ST36 on the pharmacokinetics of Schisandra lignans including schisandrin, deoxyschisandrin and schisandrin B after intragastric administration of Schisandra chinensis (SC) in rats. Methods Twelve male Sprague-Dawley rats were randomly divided into two study groups: SC and SC+acupuncture. Rats in both groups received intragastric SC extract at 5.0 g/kg. Rats in the SC+acupuncture group additionally received acupuncture stimulation at ST36 for 30 min after SC administration. Acupuncture needles were rotated bilaterally for 1 min, left in situ for 20 min, then electrically stimulated for 10 min at 50 Hz frequency and 1–3 mA intensity. A sensitive and specific high performance liquid chromatography electrospray tandem mass spectrometry procedure was developed and validated for simultaneous analysis of three bioactive lignans (schisandrin, deoxyschisandrin and schisandrin B) in rat plasma. Results There were significant differences (p<0.05) between the two study groups in various pharmacokinetic parameters. Area under the plasma concentration–time curve (AUC0–t), area under the plasma concentration–time curve to time infinity (AUC0–∞) and peak plasma concentration (Cmax) for schisandrin, absorption half-life (T1/2α) and AUC0–t for deoxyschisandrin, and Cmax for schisandrin B were increased in the SC+acupuncture group compared with the SC group. T1/2α for schisandrin B only and time to peak concentration (Tmax) for all three lignans were reduced following acupuncture. Conclusions Acupuncture stimulation at ST36 affects the pharmacokinetics of SC in rats. Acupuncture may have a beneficial role in promoting the absorption of lignans from extracts of SC.

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Simultaneous Determination of Three Alkaloids in Wutou Decoction in Rat Plasma Via the UPLC–MS/MS Method and its Application in Pharmacokinetic Study

Current Pharmaceutical Analysis ◽

10.2174/1573412915666181127151626 ◽

2020 ◽

Vol 16 (5) ◽

pp. 558-563

Author(s):

WU Jian ◽

JI Yu-bin ◽

Liu Ying-jie ◽

XU Ying ◽

Zheng Wei ◽

...

Keyword(s):

Electrospray Ionization ◽

Pharmacokinetic Study ◽

Multiple Reaction Monitoring ◽

Ultra Performance Liquid Chromatography ◽

Rat Plasma ◽

Pharmacokinetic Parameters ◽

Intragastric Administration ◽

Highly Sensitive ◽

Pharmacokinetic Properties

Introduction: Wutou decoction has been wildly applied for the treatment of RA in China for several thousand years. Methods: This study aims to develop a highly sensitive and specific ultra performance liquid chromatography coupled with tandem mass spectrometry and electrospray ionization (UPLC-ESI-MS/MS) method to explore the pharmacokinetic properties of three representative bioactive alkaloids after intragastric administration of Wutou decoction in rats. Chromatographic separation was performed on a C18 column under the Multiple Reaction Monitoring (MRM) in the positive electrospray ionization (ESI) mode. The pharmacokinetic parameters were evaluated by software DAS 3. 0. Results: The validation of the method was achieved in accordance with the FDA guidelines. The results of pharmacokinetic study showed that the in vivo concentrations of benzoylmesaconine and benzoylhypaconine were significantly higher than benzoylaconine. Our PK results showed that these three compounds were quickly absorbed after the administration of Wutou decoction, and Tmax ranged from 30 min to 45 min. Conclusion: The results of pharmacokinetic study showed that the in vivo concentrations of benzoylmesaconine and benzoylhypaconine were significantly higher than benzoylaconine. There were also similar pharmacokinetic behaviors observed among BAC, BHA, and BMA after oral administration of WTD.

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Development and Optimization of a High Sensitivity LC-MS/MS Method for the Determination of Hesperidin and Naringenin in Rat Plasma: Pharmacokinetic Approach

Molecules ◽

10.3390/molecules25184241 ◽

2020 ◽

Vol 25 (18) ◽

pp. 4241

Author(s):

Jesús Alfredo Araujo-León ◽

Rolffy Ortiz-Andrade ◽

Rivelino Armando Vera-Sánchez ◽

Julio Enrique Oney-Montalvo ◽

Tania Isolina Coral-Martínez ◽

...

Keyword(s):

Multiple Reaction Monitoring ◽

Detection Limits ◽

High Sensitivity ◽

Rat Plasma ◽

Pharmacokinetic Parameters ◽

Intragastric Administration ◽

Validation Parameters ◽

Plasma Pharmacokinetic ◽

Pharmacokinetic Approach

The purpose of this study was to develop, optimize, and fully validate a high-sensitivity methodology using UHPLC-MS/MS to simultaneously quantify hesperidin and naringenin in microsamples (100 µL) of murine plasma after intragastric administration of single pure flavonoids and a mixture. The optimization process allowed for high sensitivity with detection limits of approximately picogram order using an electrospray ionization (ESI) source in negative mode and an experiment based on multiple reaction monitoring (MRM). The validation parameters showed excellent linearity and detection limits, with a precision of less than 8% and a recovery of over 90%. This methodology was applied to compare the pharmacokinetic parameters for the administration of hesperidin and naringenin in individual form or in the form of a mixture. The results showed an absence of significant effects (p > 0.05) for Tmax and Cmax; however, the AUC presented significant differences (p < 0.05) for both flavonoids when administered as a mixture, showing an improved absorption ratio for both flavonoids.

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Ginsenoside Compound K Promotes Intestinal Peristalsis and the Pharmacokinetic of Metabolite 20(S)-Protopanaxadiol in Relation to Diarrhea

Journal of Nanomaterials ◽

10.1155/2021/5521899 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Lulu Chen ◽

Luping Zhou ◽

Xiangchang Zeng ◽

Jianwei Liao ◽

Guoping Yang ◽

...

Keyword(s):

Pharmacokinetic Parameters ◽

Intragastric Administration ◽

Potential Mechanism ◽

Compound K ◽

Traditional Herbal Medicine ◽

Colon Tissue ◽

Candidate Drug ◽

Intestinal Peristalsis ◽

Ginsenoside Compound K ◽

Rare Ginsenoside

Ginsenoside compound K (G-CK) is a rare ginsenoside originating from the traditional herbal medicine ginseng. Recently, G-CK has been found to cause diarrhea in preclinical researches as a candidate drug. This study is aimed at the potential mechanism of G-CK-induced diarrhea. In this study, we found that the treatment of G-CK significantly increased the peristaltic index (PI) with the intragastric administration of charcoal meal suspension at 90 minutes (not 30 min) after the administration of G-CK and had a clear role in promoting defecation. The Ach and 5-HT levels in colon tissue were not affected by G-CK. Additionally, the clinical trial revealed that subjects with diarrhea had lower exposure and higher Vz / F of 20(S)-protopanaxadiol (PPD) than nondiarrhea subjects, and there were no statistical differences in the pharmacokinetic parameters of G-CK between diarrhea and nondiarrhea subjects. We therefore concluded that the increased intestinal peristalsis and metabolite 20(S)-PPD were involved in G-CK-induced diarrhea.

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THE STUDY OF THE PHARMACOKINETIC PROPERTIES OF 11-DEOXYMISOPROSTOL AFTER INTRAGASTRIC ADMINISTRATION

Sechenov Medical Journal ◽

10.47093/22187332.2019.1.22-28 ◽

2019 ◽

Vol 10 (1) ◽

pp. 22-28

Author(s):

R. M. Kataeva ◽

E. F. Agletdinov ◽

K. V. Bulygin ◽

V. A. Kataev ◽

N. A. Ivanova ◽

...

Keyword(s):

Blood Plasma ◽

Laboratory Animals ◽

Array Detector ◽

Pharmacokinetic Parameters ◽

Intragastric Administration ◽

Test Substance ◽

Liquid Chromatograph ◽

Tissue Homogenates ◽

G 11 ◽

The Brain

The aim - to establish the main pharmacokinetic parameters of 11-deoxyimisoprostol after intragastric administration. Materials and methods. The experiments were performed on 410 white outbred rats - females weighing 180-220 g. 11-deoxymysoprostol was administered to rats intragastrally at a dose of 2.0 mg/kg. Blood and organs were taken for examination at 6, 12, 15, 30 minutes and hourly for 12 hours after administration. After these intervals, the concentration of the drug in the blood and tissue homogenates of laboratory animals was determined, and in the urine - every hour during the day. Chromatographic separation was carried out using a liquid chromatograph (Shimadzu, Japan LC-20 PROMI- NENCE with a diode - array detector SPD-20A).Results. 11-deoxyimisoprostol is rapidly absorbed from the gastrointestinal tract. The maximum (6.625 μg/ml) of the compound in the blood plasma is reached 15 minutes after intragastric administration. When this occurs, a simultaneous in - crease in the concentration of the metabolite - 11-deoxyimisoprostolic acid. The maximum concentration (23.547 µg/ml) of the metabolite in the blood plasma is reached 30 minutes after the administration of 11-deoxyimisoprostol. 11-deoxyimisoprostol is intensively distributed throughout the organs and tissues, while the compound has the highest aﬃnity for myometrium and liver. The smallest quantities of the test substance were found in the lungs, the brain, and the omentum. The active metabolite of 11-deoxyimisoprostol is intensively distributed in organs and tissues, while in the greatest amounts it was detected in the myometrium and the liver and kidneys. The smallest quantities of the test substance were found in the lungs, the brain, and the omentum. In the urine, 11-deoxyimisoprostolic acid is determined during the ﬁrst days of the study, with a maximum clearance of 6-8 hours after administration.Conclusion. 11-deoxyimisoprostol has a short half - life after intragastric administration (T1/2=0,550 h), which indicates the absence of cumulative properties. The nature of the pharmacokinetic curve is monoexponential.

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Evaluation of Zhenwu Decoction Effects on CYP450 Enzymes in Rats Using a Cocktail Method by UPLC-MS/MS

BioMed Research International ◽

10.1155/2020/4816209 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Li-li Hong ◽

Qian Wang ◽

Ya-ting Zhao ◽

Sheng Zhang ◽

Kai-qi Zhang ◽

...

Keyword(s):

Mrna Expression ◽

High Performance ◽

Pharmacokinetic Parameters ◽

High Dose ◽

Intragastric Administration ◽

Mixed Solution ◽

Once Daily ◽

Inductive Effects ◽

Polymerase Chain ◽

Kg Medium

This thesis is aimed at shedding light on the effects of the Zhenwu decoction (ZWD) on the activities and mRNA expressions of seven CYP450 isoenzymes. In the first step, we determined the main chemical compounds of ZWD by high-performance liquid chromatography (HPLC). Next, 48 male (SD) rats were randomly divided into the normal saline (NS) group and the ZWD low- (2.1875 g/kg), medium- (4.375 g/kg), and high- (8.75 g/kg) dose groups (12 per group). All rats were gavaged once daily for 28 consecutive days. A mixed solution of seven probe drugs was injected into 24 rats through the caudal vein after the last intragastric administration. Lastly, a validated cocktail method and real-time quantitative reverse-transcription polymerase chain reaction (RT-qPCR) were used to detect pharmacokinetic parameters and mRNA expressions, respectively. Compared with the NS group, ZWD at medium- and high-dose groups could significantly induce CYP2C6 (P<0.05) activity, while the mRNA expression (P<0.05) increased only in the high-dose group. Additionally, CYP2C11 activity was induced and consistent with mRNA expression (P<0.05). Moreover, ZWD could induce the activity of CYP3A1 (P<0.05), but the mRNA expression showed no significant differences except in high-dose groups. Additionally, ZWD has no effects on CYP1A2, CYP2B1, CYP2C7, and CYP2D2. In conclusion, the significant inductive effects of ZWD on three CYP450 isoenzymes indicated that when ZWD was coadministrated with drugs mediated by these enzymes, not only should the potential herb-drug interactions (HDIs) be observed, but the dosage adjustment and tissue drug concentration should also be considered. Furthermore, the approach described in this article can be applied to study the importance of gender, age, and disease factors to HDI prediction.

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Determination of Main Compositions in Phyllanthus Urinaria and its Effects on Cyp450 in Rats

Current Pharmaceutical Analysis ◽

10.2174/1573412915666190312160359 ◽

2020 ◽

Vol 16 (5) ◽

pp. 520-528

Author(s):

Zhennan Zhang ◽

Zhe Sun ◽

Yaozhen Ye ◽

Xianqin Wang

Keyword(s):

Dose Group ◽

Chemical Constituents ◽

Pharmacokinetic Parameters ◽

Control Group ◽

High Dose ◽

Intragastric Administration ◽

Chemical Compositions ◽

Extract Solution ◽

Phyllanthus Urinaria ◽

Cyp450 Enzyme

Background: Phyllanthus urinaria, a traditional herbal medicine, has aroused widespread concern at home and abroad. However, there are few studies on the effects of Phyllanthus urinaria on CYP450. Therefore, this study aims to explore the main chemical compositions of Phyllanthus urinaria and its effect on the activity of CYP450 enzyme in rats. Methods: Acetonitrile and 0.1% Trifluoroacetic Acid (TFA) were used as mobile phase, along with the application of gradient elution to simultaneously determine the main chemical constituents in Phyllanthus urinaria by HPLC (r2>0.999). Sprague-Dawley (SD) rats, randomly divided into control group, low-dose group and high-dose group, were treated with normal saline and different doses of Phyllanthus urinaria extract solution, respectively. Additionally, the rats were given intragastric administration of cocktail probe (specific substrates of CYP450 isoenzyme) at 15th day; the plasma was collected by tail vein at various times. Furthermore, the UPLC-MS/MS method (r2>0.99) was used to detect the probe concentration, along with the evaluation of the activity of CYP450 enzyme according to the pharmacokinetic parameters of the probe. Results: Gallic acid, 3, 4-dihydroxybenzoic acid, caffeic acid, corilagin and ellagic acid were found in the Phyllanthus urinaria extract solution by HPLC. Compared with the control group, the metabolism of bupropion, metoprolol, midazolam and tolbutamide slowed down significantly in the Phyllanthus urinaria group, with no significant metabolic changes in phenacetin. Conclusion: Phyllanthus urinaria could induce activity of CYP2D6, CYP2B1, CYP3A4 and CYP2C9, without exerting a significant effect on CYP1A2.

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