scholarly journals Effect of the Phragmitis Rhizoma Aqueous Extract on the Pharmacokinetics of Docetaxel in Rats

2019 ◽  
Vol 22 (5) ◽  
pp. 326-332
Author(s):  
Sarah Shin ◽  
No Soo Kim ◽  
Young Ah Kim ◽  
Hea Ry Oh ◽  
Ok-Sun Bang

Background: Traditionally, Phragmitis rhizoma has been prescribed to relive a fever, vomiting, dysuria, and constipation, and to promote secretion of fluids. In addition, recent studies have reported its efficacy as a diuretic and antiemetic. Our previous study demonstrated that the Phragmitis rhizoma aqueous extract (EPR) ameliorates docetaxel (DTX)-induced myelotoxicity. Aim and Objective: This study was aimed to investigate the effects of EPR on the pharmacokinetics of DTX in Sprague–Dawley rats. Materials & Methods: The animals received an intravenous injection of DTX (5 mg/kg) with or without oral EPR (100 mg/kg) pretreatment for 1 or 6 days. The pharmacokinetics of plasma DTX was analyzed using an ultra-performance liquid chromatography-tandem mass spectrometry system, and pharmacokinetic parameters were estimated via noncompartmental analysis. Results: Relative to the control group (DTX alone), EPR pretreatment did not affect significantly the overall profiles of plasma DTX levels. Consecutively pretreated EPR for 6 days slightly altered AUC0-t and Cmax of DTX by 122 and 145.9%, respectively, but these data did not reach the threshold of statistical significance (p > 0.05). Conclusion: These results indicate that DTX exposure may not be affected by EPR treatment at the dose level used in this study, suggesting that oral EPR can be used safely when taken with intravenously injected DTX. However, further studies under the stringent conditions are needed when chronic treatment of EPR and anticancer drug.

2021 ◽  
Vol 17 ◽  
Author(s):  
Xingxing Zhuang ◽  
Li Zhou ◽  
Renhua Miao ◽  
Shoudong Ni ◽  
Meng Li

Introduction:: Asari Radix et Rhizoma (ARR) and dried ginger (Zingiber officinalis) (DG) are often used together in drug preparations in traditional Chinese medicine (TCM) to treat respiratory diseases including cold, bronchitis and pneumonia. Previous studies suggested that ARR and/or DG may influence the pharmacokinetics of other herbal components. In the current study, we examined pharmacokinetic interactions between ARR and DG in rats after oral administration. Methods:: We developed a method based on ultra-high-performance liquid chromatography-tandem mass spectrometry to simultaneously measure serum concentrations of two active components each in ARR (L-asarinin and sesamin) and DG (6-gingerol and 6-shogaol). Adult Sprague-Dawley rats were starved overnight, then given ARR extract, DO extract, or a co-decoction of ARR and DG by gastric gavage (6 g raw material per kg body weight; n = 6 per group). Blood samples were collected prior to drug administration and at the following times (h) afterward: 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12.0 and 24.0. Pharmacokinetic parameters were compared using Student’s t test for independent samples. Results:: A simple, rapid, sensitive analytical method has been developed to detect four bioactive components simultaneously in the ARR-DG herbal pair. Pharmacokinetic parameters including Cmax, Tmax, T1/2 and AUC(0~t) were calculated using the non-compartmental model with the DAS 2.0 pharmacokinetic software. For L-asarinin, Tmax was 2.00 ± 0.00 h in ARR animals and 1.67±0.26 h in ARR-DG animals (P<0.05), T1/2 was 8.58 ± 1.75 h in ARR and 11.93 ± 2.13 h in ARR-DG (P<0.05). For 6-gingerol, Cmax was 350.48 ± 23.85 ng/mL in DG animals and 300.21 ± 20.02 ng/mL in ARR-DG (P<0.01), Tmax was 2.83 ± 0.41 h in DG and 2.17 ± 0.41 h in ARR-DG (P<0.05) and AUC(0~t) was 1.93 ± 0.15 mg/mL•h in ARR and 1.70 ± 0.15 mg/mL•h in ARR-DG (P<0.05). For 6-shogaol, Cmax was 390.28 ± 26.02 ng/mL in DG animals and 455.63 ± 31.01 ng/mL in ARR-DG (P<0.01), Tmax was 2.93 ± 0.10 h in DG and 1.92 ± 0.10 h in ARR-DG (P<0.01), T1/2 was 3.74 ± 0.29 h in DG and 3.28 ± 0.22 h in ARR-DG (P<0.01), and AUC(0~t) was 2.15 ± 0.18 mg/mL•h in DG and 2.73 ± 0.15 mg/mL•h in ARR-DG (P<0.01). Conclusions:: Pharmacokinetic interations between ARR and DG decrease Tmax, increase T1/2 but do not affect overall bioavailability of L-asarinin in ARR. The interactions in ARR-DG decrease Cmax and Tmax but increase T1/2 and AUC(0~t) of 6-gingerol in DG. The interactions increase Cmax and AUC(0~t) but decrease Tmax and T1/2 of 6- shogaol in DG. Interactions in ARR-DG do not affect the pharmacokinetics of sesamin.


2017 ◽  
Vol 61 (5) ◽  
Author(s):  
Charles S. Venuto ◽  
Marianthi Markatou ◽  
Yvonne Woolwine-Cunningham ◽  
Rosemary Furlage ◽  
Andrew J. Ocque ◽  
...  

ABSTRACT The liver is crucial to pharmacology, yet substantial knowledge gaps exist in the understanding of its basic pharmacologic processes. An improved understanding for humans requires reliable and reproducible liver sampling methods. We compared liver concentrations of paritaprevir and ritonavir in rats by using samples collected by fine-needle aspiration (FNA), core needle biopsy (CNB), and surgical resection. Thirteen Sprague-Dawley rats were evaluated, nine of which received paritaprevir/ritonavir at 30/20 mg/kg of body weight by oral gavage daily for 4 or 5 days. Drug concentrations were measured using liquid chromatography-tandem mass spectrometry on samples collected via FNA (21G needle) with 1, 3, or 5 passes (FNA1, FNA3, and FNA5); via CNB (16G needle); and via surgical resection. Drug concentrations in plasma were also assessed. Analyses included noncompartmental pharmacokinetic analysis and use of Bland-Altman techniques. All liver tissue samples had higher paritaprevir and ritonavir concentrations than those in plasma. Resected samples, considered the benchmark measure, resulted in estimations of the highest values for the pharmacokinetic parameters of exposure (maximum concentration of drug in serum [C max] and area under the concentration-time curve from 0 to 24 h [AUC0–24]) for paritaprevir and ritonavir. Bland-Altman analyses showed that the best agreement occurred between tissue resection and CNB, with 15% bias, followed by FNA3 and FNA5, with 18% bias, and FNA1 and FNA3, with a 22% bias for paritaprevir. Paritaprevir and ritonavir are highly concentrated in rat liver. Further research is needed to validate FNA sampling for humans, with the possible derivation and application of correction factors for drug concentration measurements.


2020 ◽  
Vol 32 (2) ◽  
pp. 102-106 ◽  
Author(s):  
Quan Zhou ◽  
Zhiguang Zhang ◽  
Peiwu Geng ◽  
Bingge Huang ◽  
Xianqin Wang ◽  
...  

An ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was developed and validated for quantification of ligustroflavone, which was then applied in pharmacokinetics study in rat and tissue distribution in mouse. Twelve male Sprague Dawley rats were used for pharmacokinetics after intravenous (2 or 8 mg/kg) administration of ligustroflavone, six rats for each dose. Twenty-five mice were randomly divided into 5 groups (5 mice for each group, 1 group for each time point) and received 16 mg/kg ligustroflavone via intraperitoneal administration. The linear range of the calibration curve was over 2–2000 ng/mL for ligustroflavone in rat plasma and mouse tissues. The intra-day and inter-day precision expressed in % RSD were less than 14%, and the accuracy was between 88.5% and 108.4%. The tissue distribution results indicated that ligustroflavone diffuses rapidly and widely into major organs. The level of ligustroflavone was highest in the mouse liver, followed by the kidney, spleen, and lung. The overwhelming accumulation in the liver indicated that the liver was responsible for the extensive metabolism.


2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Zhe Wang ◽  
Li Wang ◽  
Meng-ming Xia ◽  
Wei Sun ◽  
Cheng-ke Huang ◽  
...  

The objective of this work was to investigate the effect of orally administered genistein on the pharmacokinetics of imatinib and N-desmethyl imatinib in rats. Twenty-five healthy male SD (Sprague-Dawley) rats were randomly divided into five groups: A group (control group), B group (multiple dose of 100 mg/kg genistein for consecutive 15 days), C group (multiple dose of 50 mg/kg genistein for consecutive 15 days), D group (a single dose of 100 mg/kg genistein), and E group (a single dose of 50 mg/kg genistein). A single dose of imatinib is administered orally 30 min after administration of genistein (100 mg/kg or 50 mg/kg). The pharmacokinetic parameters of imatinib and N-desmethyl imatinib were calculated by DAS 3.0 software. The multiple dose of 100 mg/kg or 50 mg/kg genistein significantly (P<0.05) decreased theAUC0-tandCmaxof imatinib.AUC0-tand theCmaxof N-desmethyl imatinib were also increased, but without any significant difference. However, the single dose of 100 mg/kg or 50 mg/kg genistein has no effect on the pharmacokinetics of imatinib and N-desmethyl imatinib. Those results indicated that multiple dose of genistein (100 mg/kg or 50 mg/kg) induces the metabolism of imatinib, while single dose of genistein has no effect.


Author(s):  
Rohini Karunakaran ◽  
Ndanusa Abdullahi Hassan ◽  
Uma Sankar A ◽  
Khin Mar Aye

ABSTRACTObjective: To investigate the anti-inflammatory effect of aqueous extract of Zingiber officinale on carrageenan-induced inflammation on SpragueDawley (SD) rats.Methods: SD rats were divided into six of five groups and allowed to acclimatize for 1 week. Inflammation was induced on the animal by injecting theright hand paw with carrageenan (0.1 ml of 1%). Group 1 was given normal saline and served as a control. Group 2 was fed with food and water andserved as the carrageenan control. Group 3 was given 200 mg/kg aqueous extract of ginger, Group 4 with 400 mg/kg aqueous extract of ginger, andGroup 5 with 150 mg/kg diclofenac sodium (reference drug for inflammation).Results: The paw edema in carrageenan-induced SD rats was considerably reduced by treating with 400 mg/kg aqueous ginger extracts whencompared to the untreated SD rats (p<0.001).Conclusion: This study indicates that aqueous extract of Z. officinale possesses anti-inflammatory properties.Keywords: Anti-inflammatory, Sprague Dawley rats, Zingiber officinale, Carrageenan, Edema


2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Sebastian Molinett ◽  
Francisca Nuñez ◽  
María Alejandra Moya-León ◽  
Jessica Zúñiga-Hernández

The Chilean strawberry fruit has high content of antioxidants and polyphenols. Previous studies evidenced antioxidant properties byin vitromethods. However, the antioxidant effect and its impact as functional food on animal health have not been evaluated. In this study, rats were fed with a Chilean strawberry aqueous extract (4 g/kg of animal per day) and then subjected to LPS-induced liver injury (5 mg/kg). Transaminases and histological studies revealed a reduction in liver injury in rats fed with strawberry aqueous extract compared with the control group. Additionally, white strawberry supplementation significantly reduced the serum levels and gene expression of TNF-α, IL-6, and IL-1βcytokines compared with nonsupplemented rats. The level of F2-isoprostanes and GSH/GSSG indicated a reduction in liver oxidative stress by the consumption of strawberry aqueous extract. Altogether, the evidence suggests that dietary supplementation of rats with a Chilean white strawberry aqueous extract favours the normalization of oxidative and inflammatory responses after a liver injury induced by LPS.


Toxins ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 353 ◽  
Author(s):  
Xiaoyu Ji ◽  
Mengbi Yang ◽  
Ka Hang Or ◽  
Wan Sze Yim ◽  
Zhong Zuo

Although Radix Aconiti Lateralis (Fuzi) is an extensively used traditional Chinese medicine with promising therapeutic effects and relatively well-reported toxicities, the related toxic aconitum alkaloid concentrations in major organs after its short-term and long-term intake during clinical practice are still not known. To give a comprehensive understanding of Fuzi-induced toxicities, current study is proposed aiming to investigate the biodistribution of the six toxic alkaloids in Fuzi, namely Aconitine (AC), Hypaconitine (HA), Mesaconitine (MA), Benzoylaconine (BAC), Benzoylhypaconine (BHA) and Benzoylmesaconine (BMA), after its oral administrations at clinically relevant dosing regimen. A ultra-performance liquid chromatography-tandem mass spectrometry (UPLC–MS/MS) method was developed and validated for simultaneous quantification of six toxic alkaloids in plasma, urine and major organs of Sprague Dawley rats after oral administrations of two commonly used Fuzi preparations, namely Heishunpian and Paofupian, at their clinically relevant dose for single and 15-days. Among the studied toxic alkaloids and organs, BMA demonstrated the highest concentrations in all studied organs with liver containing the highest amount of the studied alkaloids, indicating their potential hepatotoxicity. Moreover, tissue accumulation of toxic alkaloids after multiple dose was observed, suggesting the needs for dose adjustment and more attention to the toxicities induced by chronic use of Fuzi in patients.


PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3693 ◽  
Author(s):  
Junli Jiang ◽  
Bin Wang ◽  
Zhaoqiong Zhu ◽  
Jun Yang ◽  
Jin Liu ◽  
...  

Background Because etomidate induces prolonged adrenal suppression, even following a single bolus, its use as an infused anesthetic is limited. Our previous study indicated that a single administration of the novel etomidate analog methoxyethyletomidate hydrochloride (ET-26-HCl) shows little suppression of adrenocortical function. The aims of the present study were to (1) determine the minimum infusion rate of ET-26-HCl and compare it with those for etomidate and cyclopropyl-methoxycarbonylmetomidate (CPMM), a rapidly metabolized etomidate analog that is currently in clinical trials and (2) to evaluate adrenocortical function after a continuous infusion of ET-26-HCl as part of a broader study investigating whether this etomidate analog is suitable for long infusion in the maintenance of anesthesia. Method The up-and-down method was used to determine the minimum infusion rates for ET-26-HCl, etomidate and CPMM. Sprague-Dawley rats (n = 32) were then randomly divided into four groups: etomidate, ET-26-HCl, CPMM, and vehicle control. Rats in each group were infused for 60 min with one of the drugs at its predetermined minimum infusion rate. Blood samples were drawn initially and then every 30 min after drug infusion to determine the adrenocorticotropic hormone-stimulated concentration of serum corticosterone as a measure of adrenocortical function. Results The minimum infusion rates for etomidate, ET-26-HCl and CPMM were 0.29, 0.62, and 0.95 mg/kg/min, respectively. Compared with controls, etomidate decreased serum corticosterone, as expected, whereas serum corticosterone concentrations following infusion with the etomidate analogs ET-26-HCl or CPMM were not significantly different from those in the control group. Conclusion The corticosterone concentrations tended to be reduced for the first hour following ET-26-HCl infusion (as compared to vehicle infusion); however, this reduction did not reach statistical significance. Thus, further studies are warranted examining the practicability of using ET-26-HCl as an infused anesthetic.


2019 ◽  
Vol 13 (03) ◽  
pp. 251-254
Author(s):  
Seth Kwabena Amponsah ◽  
Kwabena Frimpong-Manso Opuni ◽  
Kwabena Aboagye Antwi ◽  
Victor Pouzuing Kunkpeh

Introduction: In most resource-poor settings, amikacin is normally co-administered with aminophylline among preterm newborns with infection and apnea of prematurity. There is the likelihood of an interaction between concurrently administered amikacin that is excreted almost solely via kidneys, and aminophylline, which is known to increase filtration fraction. The aim of this study was to evaluate the effect of aminophylline on the pharmacokinetics of amikacin using an animal model. Methodology: Twelve male Sprague-Dawley rats (7 – 8 weeks old) were put into 2 equal groups. The test group received amikacin (10 mg/kg/day) with aminophylline (5 mg/kg/day) via the intraperitoneal route, and the control group received only amikacin (10 mg/kg/day) via the same route. On Day 4, after daily administration of drugs, tail vein blood samples were collected at different time points. Serum samples at each time point for each group were pooled and analyzed by fluorescence polarization immunoassay. Non-compartment pharmacokinetic analysis was used to estimate pharmacokinetic parameters. Area under the concentration-time curves (AUCs) were extrapolated from time 0 to infinity (AUC0→∞). Elimination rate constant (Ke) and elimination half-life (t1/2e) were also estimated. Results: Pharmacokinetic parameters of the control group (amikacin only) vis-a-vis the test group were as follows: Cmax; 42.4 μmol/L vs 19.0 μmol/L, AUC0→∞; 84.9 μmol/L/h vs 41.4 μmol/L/h, Ke; 0.12 hours-1 vs 0.24 hours-1, and t1/2; 5.87 hours vs 2.88 hours, respectively. Conclusion: This study suggests possible interaction between aminophylline and amikacin. However, further studies need to be conducted in humans to ascertain this finding.


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