scholarly journals Pharmacokinetic Comparison of 20(R)- and 20(S)-Ginsenoside Rh1 and 20(R)- and 20(S)-Ginsenoside Rg3 in Rat Plasma following Oral Administration of Radix Ginseng Rubra and Sheng-Mai-San Extracts

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Xiaomei Fan ◽  
Yan Xu ◽  
Danni Zhu ◽  
Yibing Ji
Keyword(s):  
Oral Administration ◽  
Rat Plasma ◽  
Pharmacokinetic Parameters ◽  
Spectrometric Method ◽  
Pharmacokinetic Studies ◽  
Mass Spectrometric Method ◽  
Ginsenoside Rg3 ◽  
Radix Ginseng

Ginsenosides Rh1 and Rg3, as the main bioactive components from Ginseng, are effective for prevention and treatment of cardiovascular diseases. Sheng-Mai-San (SMS), a classical complex prescription of traditional Chinese medicines, is composed of Radix Ginseng Rubra, Fructus Schisandrae, and Radix Ophiopogonis. In this research, a sensitive and specific liquid chromatography-mass spectrometric method was developed and validated for stereoselective determination and pharmacokinetic studies of 20(R)- and 20(S)-ginsenoside Rh1 and 20(R)- and 20(S)-ginsenoside Rg3 epimers in rat plasma after oral administration of Radix Ginseng Rubra or SMS extracts. The main pharmacokinetic parameters including Tmax, Cmax, t1/2, and AUC were calculated by noncompartment model. Compared with Radix Ginseng Rubra, SMS could significantly increase the content of ginsenosides Rh1 and Rg3 in the decocting process. Ginsenosides Rh1 and Rg3 following SMS treatment displayed higher Cmax, AUC(0–t), and AUC0–∞ and longer t1/2 and tmax except for 20(R)-Rh1 in rat plasma. The results indicated SMS compound compatibility could influence the dissolution in vitro and the pharmacokinetic behaviors in vivo of ginsenosides Rh1 and Rg3, suggesting pharmacokinetic drug-drug interactions between ginsenosides Rh1 and Rg3 and other ingredients from Fructus Schisandrae and Radix Ophiopogonis. This study would provide valuable information for drug development and clinical application of SMS.

scholarly journals Assessment of Pharmacokinetics and Metabolism Profiles of SCH 58261 in Rats Using Liquid Chromatography–Mass Spectrometric Method

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2209 ◽  
Author(s):  
Yuri Park ◽  
Min-Ho Park ◽  
Jin-Ju Byeon ◽  
Seok-Ho Shin ◽  
Byeong ill Lee ◽  
...  
Keyword(s):  
Bile Duct ◽  
Oral Administration ◽  
The Body ◽  
Metabolic Stability ◽  
In Vivo Model ◽  
Spectrometric Method ◽  
Mass Spectrometric Method ◽  
Sch 58261

5-Amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c) pyrimidine (SCH 58261) is one of the new chemical entities that has been developed as an adenosine A2A receptor antagonist. Although SCH 58261 has been reported to be beneficial, there is little information about SCH 58261 from a drug metabolism or pharmacokinetics perspective. This study describes the metabolism and pharmacokinetic properties of SCH 58261 in order to understand its behaviors in vivo. Rats were used as the in vivo model species. First, an LC–MS/MS method was developed for the determination of SCH 58261 in rat plasma. A GastroPlus™ simulation, in vitro microsomal metabolic stability, and bile duct-cannulated studies were also performed to understand its pharmacokinetic profile. The parameter sensitivity analysis of GastroPlus™ was used to examine the factors that influence exposure when the drug is orally administered. The factors are as follows: permeability, systemic clearance, renal clearance, and liver first-pass effect. In vitro microsomal metabolic stability indicates how much the drug is metabolized. The extrapolated hepatic clearance value of SCH 58261 was 39.97 mL/min/kg, indicating that the drug is greatly affected by hepatic metabolism. In vitro microsomal metabolite identification studies revealed that metabolites produce oxidized and ketone-formed metabolites via metabolic enzymes in the liver. The bile duct-cannulated rat study, after oral administration of SCH 58261, showed that a significant amount of the drug was excreted in feces. These results imply that the drug is not absorbed well in the body after oral administration. Taken together, SCH 58261 showed quite a low bioavailability when administered orally and this was likely due to significantly limited absorption, as well as high metabolism in vivo.

Development of An Antidiabetic Phytocomposite Loaded Phytoceutical Formulation, Its Quality Control and Pharmacokinetic Studies and Establishing In Vitro- In Vivo Correlation

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
De Baishakhi ◽  
Bhandari Koushik ◽  
Katakam Prakash ◽  
Adiki Shanta ◽  
Mitra Analava
Keyword(s):  
Rat Plasma ◽  
Angle Of Repose ◽  
Fickian Diffusion ◽  
Core Material ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Natural Polymers ◽  
Gum Karaya

This study reports the development of solid oral phytoceutical formulations with Phytocomposite (PHC), an antidiabetic poly herbal preparation as the active core material. Spherical, monolithic PHC microspheres of size range (10 -100 µm) were obtained with Hausner ratio, Carr’s index and angle of repose of 1.141± 0.010, 12.418±0.769 and 25.17±0.96 respectively. Encapsulation efficiency amongst different batches (F1-F5) ranged from 96.8- 100.7, with 99% release profile up to 12h. Conventional and sustained release tablets were prepared by direct compression and compatibility amongst polymers and the PHC checked by FTIR studies. Natural polymers viz. gum kondagogu, gum karaya, Aegle marmelos gum were used as release retardant. Optimized batch of conventional tablets (F6) showed 99.8 % release in 35 min and optimized batch of PHC-SR tablets (F12) showed 99.9% release at 12th hr, both followed zero order kinetics and non-Fickian diffusion. These optimized formulations were subjected to stability studies and the similarity factors (f2) of the conventional and SR tablets were 88.75 and 66.76 respectively. Pharmacokinetic parameters of three formulations in rat plasma were analyzed by PK Solver 2.0. In vitro-in vivo correlation (IVIVC) of three different formulations showed Level A correlation in all cases.

scholarly journals Design and Characterization of Combinational Domperidone-Famotidine Floating Drug Delivery System - In vitro and In vivo studies

2021 ◽  
Vol 62 (2) ◽  
pp. 144-162
Author(s):  
Mounika Chidurala ◽  
Raveendra Reddy J
Keyword(s):  
Drug Release ◽  
Oral Administration ◽  
Quality By Design ◽  
Release Kinetics ◽  
Cost Effective ◽  
Fickian Diffusion ◽  
In Vivo Studies ◽  
Pharmacokinetic Studies

Introduction: The drawbacks assosiated with oral administration of drugscan be controlled or minimized by gastro retentive formulations that remain buoyant within the stomach for an extended time by providing prolonged gastric retention and releasethe drug in an exceedingly extended manner thereby improving bioavailability. The current research was to develop and optimize Domperidone and Famotidine floating tablets with extended release by Quality by Design approach. Method: Based on QTPP (Quality Target Product Profile), CQAs (Critical Quality Attributes)wereidentified. Risk analysis by the evaluation of formulation and process parameters showed that optimizing the levels of polymers could reduce high risk to achieve the target profile. A 23factor experimental design with midpoints was selected for statistical analysis and optimization. Results: HPMC K100 and Carbopol 934P had a positive effect while ethyl cellulose demonstrated a negative effect on the selected responses. Drug release kinetics followed the first-order release with Higuchi diffusion and Fickian diffusion. Optimized formula satisfying all the required parameters was selected and evaluated. The predicted response values were in close agreement with experimental response values. Abdominal X-ray imaging after oral administration of the tablets on a healthy rabbit’s stomach confirmed the extended floating behavior with shorter lag time. In vivo, pharmacokinetic studies in rabbits revealed that the optimized formulation exhibited prolonged drug release with enhanced Cmax, tmax, AUCo-t, and t1/2 of an optimized product when compared to the marketed product. Conclusions: It has been concluded that the application of Quality by Design in the formulation and optimization reduced the number of trials to produce a cost-effective formula.

scholarly journals An LC-MS/MS Method for Simultaneous Determination of the Toxic and Active Components of Cortex Periplocae in Rat Plasma and Application to a Pharmacokinetic Study

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Zhen Li ◽  
Yang Li ◽  
Jin Li ◽  
Rui Liu ◽  
Jia Hao ◽  
...  
Keyword(s):  
Oral Administration ◽  
Multiple Reaction Monitoring ◽  
Gradient Elution ◽  
Rat Plasma ◽  
Pharmacokinetic Studies ◽  
Simple Liquid ◽  
Active Components ◽  
Limit Of Quantification ◽  
Liquid Chromatography Tandem Mass

A sensitive and simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to simultaneously determine the toxic and other active components including isovanillin, scopoletin, periplocin, periplogenin, and periplocymarin after oral administration of cortex periplocae extract to rats. Plasma samples were prepared by protein precipitation with methanol. All compounds were separated on a C18 column with gradient elution using acetonitrile and formic acid aqueous solution (0.1%, v/v) as the mobile phase at a flow rate of 0.3 mL/min. The detection of all compounds was accomplished by multiple-reaction monitoring (MRM) in the positive electrospray ionization mode. The LC-MS/MS method exhibited good linearity for five analytes. The lower limit of quantification (LLOQ) was 0.48 ng/mL for scopoletin, periplogenin, and periplocymarin; 2.4 ng/mL for isovanillin and periplocin. The extraction recoveries of all compounds were more than 90% and the RSDs were below 10%. It was found that the absorption of scopoletin and periplocin was rapid in vivo after oral administration of cortex periplocae extract. Furthermore, periplocymarin possessed abundant plasma exposure. The results demonstrated that the validated method was efficiently applied for the pharmacokinetic studies of isovanillin, scopoletin, periplocin, periplogenin, and periplocymarin after oral administration of cortex periplocae extract.

scholarly journals Profiling and Pharmacokinetic Studies of Alkaloids in Rats After Oral Administration of Zanthoxylum nitidum Decoction by UPLC-Q-TOF-MS/MS and HPLC-MS/MS

Molecules ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 585 ◽  
Author(s):  
Aihua Huang ◽  
Yuguang Chi ◽  
Jiawei Liu ◽  
Mincun Wang ◽  
Jialiang Qin ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Oral Administration ◽  
High Performance ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Pharmacokinetic Studies ◽  
Flight Mass Spectrometry ◽  
Zanthoxylum Nitidum

Zanthoxylum nitidum (Roxb.) DC (Rutaceae), called as “liangmianzhen” in China, is well known for its anti-inflammation and analgesic effect. Alkaloids are its main active constituents. However, little has been known about the absorption of main alkaloids in vivo. In this study, an ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry was employed for identification of absorbed alkaloids in rats after oral administration of Z. nitidum decoction. By analyzing the fragmentation patterns, a total of nineteen alkaloids were exactly or tentatively identified in rat plasma after treatment, of which magnoflorine, α-allocryptopine, and skimmianine are dominant. Moreover, a high performance liquid chromatography coupled mass spectrometry method was developed for simultaneous quantification of magnoflorine, α-allocryptopine, and skimmianine, and successfully applied to pharmacokinetic study in rats after oral administration of Z. nitidum decoction. The research would contribute to comprehensive understanding of the material basis and function mechanism of Z. nitidum decoction.

scholarly journals Enhanced Dissolution and Oral Bioavailability of Cyclosporine A: Microspheres Based on αβ-Cyclodextrins Polymers

Pharmaceutics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 285 ◽  
Author(s):  
Malika Lahiani-Skiba ◽  
Francois Hallouard ◽  
Frederic Bounoure ◽  
Nicolas Milon ◽  
Youness Karrout ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Secondary Structure ◽  
Oral Administration ◽  
Drug Delivery System ◽  
Delivery System ◽  
Cyclosporine A ◽  
Polymer Mixture ◽  
Pharmacokinetic Parameters

Cyclosporine (CsA) has a selective property of suppressing various T-lymphocyte functions. This is of utmost importance in preventing allograft rejection by several organ transplantations, as well as in the treatment of systemic and local autoimmune disorders. However, the poor water solubility of CsA can be a major hurdle for its absorption into the blood stream, which leads to low bioavailability and thus less efficacy. The aim of this study was to prepare, characterize, and evaluate in vitro as well as in vivo, the potential of the innovative CsA drug delivery system. The latter contains CsA in spherical amorphous solid dispersion (SASD) which is embedded in an original α-cyclodextrin and β-cyclodextrin polymer mixture (Poly-αβ-CD) as a multifunctional amorphous carrier. The new developed SASD formulation showed that CsA was molecularly dispersed in αβ-cyclodextrins in an amorphous form, as was confirmed by physicochemical characterization studies. Interestingly, the peptide secondary structure, and thus, the drug activity was not impacted by the preparation of SASD as was shown by circular dichroism. Furthermore, the in vitro CsA release profile kinetics was almost identical to the commercially available product Neoral®. This study presents the first in vivo proof-of-concept for a novel drug delivery system based on Poly-αβ-CD containing CsA, with SASD allowing for increased bioavailibility. The pharmacokinetic parameters of cyclosporine A from the spherical spray-dried dispersion formulation was demonstrated in a “rat” animal model. For comparison, the commercially available Neoral® was studied. Importantly, the pharmacokinetic parameters were improved by extending Tmax from 2 to 3 h after the oral administration in rats, and eventually preventing the enterohepatic circulation. All these results clearly demonstrate the improved pharmacokinetic parameters and enhanced bioavailability of CsA in the new developed drug delivery system. These data demonstrated the superiority of the newly developed Poly-αβ-CD formulation for oral administration of the poorly soluble CsA in vivo without altering its secondary structure. Poly-αβ-CD can be a very useful tool for the oral administration of poorly water-soluble drugs.

scholarly journals Formulation, In Vitro and In Vivo Evaluation of Gefitinib Solid Dispersions Prepared Using Different Techniques

Processes ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 1210
Author(s):  
Sultan Alshehri ◽  
Abdullah Alanazi ◽  
Ehab M. Elzayat ◽  
Mohammad A. Altamimi ◽  
Syed S. Imam ◽  
...  
Keyword(s):  
Oral Absorption ◽  
Solid Dispersions ◽  
Water Soluble ◽  
In Vitro Dissolution ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
In Vivo Evaluation ◽  
Significant Release

Gefitinib (Gef) is a poorly water-soluble antitumor drug, which shows poor absorption/bioavailability after oral administration. Therefore, this study was carried out to develop Gef solid dispersions (SDs) using different carriers and different techniques in order to enhance its dissolution and oral absorption/bioavailability. Various SD formulations of Gef were established using fusion and microwave methods utilizing Soluplus, Kollidone VA64, and polyethylene glycol 4000 (PEG 4000) as the carriers. Developed SDs of Gef were characterized physicochemically and evaluated for in vitro dissolution and in vivo pharmacokinetic studies. The physicochemical evaluation revealed the formation of Gef SDs using fusion and microwave methods. In vitro dissolution studies indicated significant release of Gef from all SDs compared to the pure Gef. Optimized SD of Gef (S2-MW) presented significant release of Gef (82.10%) compared with pure Gef (21.23%). The optimized Gef SD (S2) was subjected to in vivo pharmacokinetic evaluation in comparison with pure Gef in rats. The results indicated significant enhancement in various pharmacokinetic parameters of Gef from an optimized SD S2 compared to the pure Gef. In addition, Gef-SD S2 resulted in remarkable improvement in bioavailability compared to the pure Gef. Overall, this study suggested that the prepared Gef-SD by microwave method showed marked enhancement in dissolution and bioavailability.

scholarly journals In vitro and in vivo pharmacokinetic characterization of LMT-28 as a novel small molecular interleukin-6 inhibitor

2020 ◽  
Vol 33 (4) ◽  
pp. 670-677
Author(s):  
Sung-Hoon Ahn ◽  
Tae-Hwe Heo ◽  
Hyun-Sik Jun ◽  
Yongseok Choi
Keyword(s):  
Mdck Cell ◽  
Interleukin 6 ◽  
Cell Permeability ◽  
Oral Drug ◽  
Drug Candidate ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Pharmacokinetic Properties

Objective: Interleukin-6 (IL-6) is a T cell-derived B cell stimulating factor which plays an important role in inflammatory diseases. In this study, the pharmacokinetic properties of LMT-28 including physicochemical property, <i>in vitro</i> liver microsomal stability and an <i>in vivo</i> pharmacokinetic study using BALB/c mice were characterized.Methods: LMT-28 has been synthesized and is being developed as a novel therapeutic IL-6 inhibitor. The physicochemical properties and <i>in vitro</i> pharmacokinetic profiles such as liver microsomal stability and Madin-Darby canine kidney (MDCK) cell permeability assay were examined. For <i>in vivo</i> pharmacokinetic studies, pharmacokinetic parameters using BALB/c mice were calculated.Results: The logarithm of the partition coefficient value (LogP; 3.65) and the apparent permeability coefficient values (P<sub>app</sub>; 9.7×10<sup>–6</sup> cm/s) showed that LMT-28 possesses a moderate-high cell permeability property across MDCK cell monolayers. The plasma protein binding rate of LMT-28 was 92.4% and mostly bound to serum albumin. The metabolic half-life (t<sub>1/2</sub>) values of LMT-28 were 15.3 min for rat and 21.9 min for human at the concentration 1 μM. The area under the plasma drug concentration-time curve and C<sub>max</sub> after oral administration (5 mg/kg) of LMT-28 were 302±209 h∙ng/mL and 137±100 ng/mL, respectively.Conclusion: These data suggest that LMT-28 may have good physicochemical and pharmacokinetic properties and may be a novel oral drug candidate as the first synthetic IL-6 inhibitor to ameliorate mammalian inflammation.

Simultaneous Determination of Four Bioactive Flavonoids in Rat Plasma by UPLC–MS/MS and Comparative Pharmacokinetic Study after Oral Administration of Danyikangtai Powder and Three Compatibilities

2020 ◽  
Vol 16 ◽  
Author(s):  
Yihe Huang ◽  
Yanhui Zhao ◽  
Yumeng Zhang ◽  
Lin Sun ◽  
Chunjie Zhao ◽  
...  
Keyword(s):  
Oral Administration ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Drug Candidate ◽  
Pharmacokinetic Parameters ◽  
Simultaneous Treatment ◽  
Scutellariae Radix

Background: Danyikangtai powder, a traditional Chinese medicine (TCM) formula, shows promise to become a novel drug candidate for the simultaneous treatment of chronic cholecystitis and chronic pancreatitis. However, the pharmacokinetic behavior of Danyikangtai powder remains unclear. Objective: We investigated the comparative pharmacokinetics of four flavonoids in rats after oral administration of Danyikangtai powder and three compatibilites. Materials and methods: The comparative pharmacokinetics was studied by ultra performance liquid chromatography tandem mass spectrometry (UPLC–MS/MS). Chromatographic separation was performed on an Universil XB-C18 column with a gradient mobile phase containing 0.1% (v/v) aqueous formic acid and acetonitrile. All analytes and internal standard were quantitated in the multiple reaction monitoring mode with a positive electrospray ionization interface. Results and discussion: Danyikangtai powder and Scutellariae radix have similar pharmacokinetic behaviors in rats after oral administration. However, the elimination of four flavonoids in rats after oral administration of Danyikangtai powder was accelerated, which was possibly related to the reduction of the potential hepatotoxicity of Scutellariae radix. The varying degrees of change in pharmacokinetic parameters after oral administration of different herb combinations suggested that herb–herb interactions occurred in vivo. Conclusions: This study will be helpful to reveal the safety, rational and mechanism of Danyikangtai powder formula compatibility, thereby providing pre-clinical research data for its new drug development and guidance for its rational clinical application.

scholarly journals Identification and Pharmacokinetic Studies on Complanatuside and Its Major Metabolites in Rats by UHPLC-Q-TOF-MS/MS and LC-MS/MS

Molecules ◽  
2018 ◽  
Vol 24 (1) ◽  
pp. 71 ◽  
Author(s):  
Yu-Feng Yao ◽  
Chao-Zhan Lin ◽  
Fang-Le Liu ◽  
Run-Jing Zhang ◽  
Qiu-Yu Zhang ◽  
...  
Keyword(s):  
Oral Administration ◽  
Degradation Products ◽  
Plasma Concentrations ◽  
Rat Plasma ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Studies ◽  
Maximum Plasma ◽  
Time Curve ◽  
Tof Ms

The metabolic and pharmacokinetic studies on complanatuside, a quality marker of a Chinese materia medicatonic, Semen Astragali Complanati, were carried out. The UHPLC-Q-TOF/MS (ultra-high performance liquid chromatography coupled with electrospray ionization tandem quadrupole-time-of-flight mass spectrometry) method was applied to identify the metabolites of complanatuside in rat plasma, bile, stool, and urine after oral administration at the dosage of 72 mg/kg. Up to 34 metabolites (parent, 2 metabolites of the parent drug, and 31 metabolites of the degradation products) were observed, including processes of demethylation, hydroxylation, glucuronidation, sulfonation, and dehydration. The results indicated glucuronidation and sulfonation as major metabolic pathways of complanatuside in vivo. Meanwhile, a HPLC-MS method to quantify complanatuside and its two major metabolites—rhamnocitrin 3-O-β-glc and rhamnocitrin—in rat plasma for the pharmacokinetic analysis was developed and validated. The Tmax (time to reach the maximum drug concentration) of the above three compounds were 1 h, 3 h, and 5.3 h, respectively, while the Cmax (maximum plasma concentrations)were 119.15 ng/mL, 111.64 ng/mL, and 1122.18 ng/mL, and AUC(0-t) (area under the plasma concentration-time curve) was 143.52 µg/L·h, 381.73 µg/L·h, and 6540.14 µg/L·h, accordingly. The pharmacokinetic characteristics of complanatuside and its two metabolites suggested that complanatuside rapidly metabolized in vivo, while its metabolites—rhamnocitrin—was the main existent form in rat plasma after oral administration. The results of intracorporal processes, existing forms, and pharmacokinetic characteristics of complanatuside in rats supported its low bioavailability.

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