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1.
PeerJ ; 11: e16051, 2023.
Article in English | MEDLINE | ID: mdl-37719112

ABSTRACT

Since the combination of anticancer drugs and opioids is very common, apatinib and tramadol are likely to be used in combination clinically. This study evaluated the effects of apatinib on the pharmacokinetics of tramadol and its main metabolite O-desmethyltramadol in Sprague-Dawley (SD) rats and the inhibitory effects of apatinib on tramadol in rat liver microsomes (RLMs), human liver microsomes (HLMs) and recombinant human CYP2D6.1. The samples were determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The in vivo results showed that compared with the control group, apatinib increased the AUC(0-t), AUC(0-∞) and Cmax values of tramadol and O-desmethyltramadol, and decreased the values of VZ/F and CLz/F. In addition, the MRT(0-t), MRT(0-∞) values of O-desmethyltramadol were increased. In vitro, apatinib inhibited the metabolism of tramadol by a mixed way with IC50 of 1.927 µM in RLMs, 2.039 µM in HLMs and 15.32 µM in CYP2D6.1. In summary, according to our findings, apatinib has a strong in vitro inhibitory effect on tramadol, and apatinib can increase the analgesic effect of tramadol and O-desmethyltramadol in rats.


Subject(s)
Tramadol , Humans , Rats , Animals , Tramadol/pharmacology , Chromatography, Liquid , Cytochrome P-450 CYP2D6 , Rats, Sprague-Dawley , Tandem Mass Spectrometry , Microsomes, Liver
2.
BMC Chem ; 17(1): 107, 2023 Aug 30.
Article in English | MEDLINE | ID: mdl-37649082

ABSTRACT

BACKGROUND: This study establishes a UHPLC‒MS/MS method for the detection of zanubrutinib and explores its interaction with fluconazole and isavuconazole in rats. METHODS: A protein precipitation method using acetonitrile was used to prepare plasma samples using ibrutinib as an internal standard. Chromatographic separation and mass spectrometric detection of the analytes and internal standards were performed on a Shimadzu 8040 UHPLC‒MS/MS equipped with a Shim-pack velox C18 column (2.1 × 50 mm, 2.7 µm). Methanol and 0.1% formic acid-water were used as mobile phases. Intraday and interday precision and accuracy, extraction recoveries, and matrix effects of this method were determined. The linearity and sample stability of the method were assessed. Eighteen male Sprague‒Dawley (SD) rats were randomly divided into three groups with zanubrutinib (30 mg/kg) alone, zanubrutinib in combination with fluconazole (20 mg/kg) or zanubrutinib in combination with isavuconazole (20 mg/kg). Blood samples (200 µL) were collected at designated time points (ten evenly distributed time points within 12 h). The concentration of zanubrutinib was determined using the UHPLC‒MS/MS method developed in this study. RESULTS: The typical fragment ions were m/z 472.15 → 290.00 for zanubrutinib and m/z 441.20 → 138.10 for ibrutinib (IS). The range of the standard curve was 1-1000 ng/mL with a regressive coefficient (R2) of 0.999. The recoveries and matrix effects were 91.9-98.2% and 97.5-106.3%, respectively, at different concentration levels. The values for intra- and interday RSD% were lower than 9.8% and 5.8%, respectively. The RSD% value was less than 10.3%, and the RE% value was less than ± 4.0% under different storage conditions. Analysis of pharmacokinetic results suggested that coadministration with isavuconazole or fluconazole significantly increased the area under the curve (1081.67 ± 43.81 vs. 1267.55 ± 79.35 vs. 1721.61 ± 219.36), peak plasma concentration (332.00 ± 52.79 vs. 396.05 ± 37.19 vs. 494.51 ± 130.68), and time to peak (1.83 ± 0.41 vs. 2.00 ± 0.00 vs. 2.17 ± 0.41) compared to zanubrutinib alone. CONCLUSION: This study provides information to understand the metabolism of zanubrutinib with concurrent use with isavuconazole or fluconazole, and further clinical trials are needed to validate the results in animals.

3.
ACS Appl Mater Interfaces ; 15(10): 13565-13575, 2023 Mar 15.
Article in English | MEDLINE | ID: mdl-36861486

ABSTRACT

Electromagnetic radiation and noise pollution are two of the four major environmental pollution sources. Although various materials with excellent microwave absorption performances or sound absorption properties have been manufactured, it is still a great challenge to design materials with both microwave absorption and sound absorption abilities due to different energy consumption mechanisms. Herein, a combination strategy based on structural engineering was proposed to develop bi-functional hierarchical Fe/C hollow microspheres composed of centripetal Fe/C nanosheets. Both of the interconnected channels created by multiple gaps among the adjacent Fe/C nanosheets and the hollow structure have positive effects on the absorbing performances by promoting the penetration of microwaves and acoustic waves and prolonging action time between microwave energy and acoustic energy with materials. In addition, a polymer-protection strategy and a high-temperature reduction process were applied to keep this unique morphology and further improve the performances of the composite. As a result, the optimized hierarchical Fe/C-500 hollow composite exhibits a wide effective absorption bandwidth of 7.52 GHz (10.48-18.00 GHz) at only 1.75 mm. Furthermore, the Fe/C-500 composite can effectively absorb sound wave in the frequency of 1209-3307 Hz, basically including part of the low frequency range (<2000 Hz) and most of the medium frequency range (2000-3500 Hz), and has 90% absorption of sound at 1721-1962 Hz. This work puts new insight into the engineering and development of microwave absorption-sound absorption-integrated functional materials with promising applications.

4.
Front Pharmacol ; 13: 960311, 2022.
Article in English | MEDLINE | ID: mdl-35935882

ABSTRACT

Almonertinib was approved for the first-line treatment of advanced NSCLC patients with EGFR-TKI-sensitive genetic mutations by National Medical Products Administration (NMPA) in 2021.The purpose of this study was to establish and validate a fast, accurate, stable and facile ultra-performance liquid chromatography-tandem mass spectrometry method for the quantification of almonertinib in rat plasma, it was employed to explore the effect of Paxlovid on the pharmacokinetics of almonertinib in rats. Zanubrutinib was used as an internal standard (IS), and the plasma samples were prepared by the protein precipitation method using acetonitrile. Chromatographic separation was carried out on a Shimadzu LC-20AT ultra-performance liquid chromatography system using a Shim-pack velox C18 (2.1× 50 mm, 2.7 µM) column. The mobile phase consisted of methanol and 0.1% formic acid-water. Mass spectrum analysis was executed using Shimadzu 8040 Triple quadrupole mass spectrometry. The precursor and product ions of the analyte and internal standard were detected in multiple reaction monitoring (MRM) mode. The typical fragment ions were m/z 526.20 → 72.10 for almonertinib and m/z 472.15 → 290.00 for zanubrutinib (IS). The method was validated to have good linearity for quantifying almonertinib in rat plasma from 0.1-1000 ng/ml (R2 = 0.999), and the LLOQ was 0.1 ng/ml. The validity of this method was sufficiently verified for selectivity, specificity, extraction recovery, matrix effect, accuracy, precision and stability. The validated UHPLC-MS/MS method was successfully applied to the drug interaction study of almonertinib with Paxlovid in rats. Paxlovid significantly inhibits the metabolism of almonertinib and increased the exposure of almonertinib. This study can help us to understand the metabolic profile of almonertinib better, and further human trials should be conducted to validate the results.

5.
Dalton Trans ; 51(22): 8705-8713, 2022 Jun 07.
Article in English | MEDLINE | ID: mdl-35611814

ABSTRACT

Owing to their unique electromagnetic properties and structure anisotropy, two-dimensional (2D) magnetic metal flakes are attracting special attention for applications as microwave absorption materials. However, the conductive network formed by the connected metal flakes may lead to impedance mismatching and reduced performance. In this study, a facile and rational strategy was developed to fabricate yolk-shell-structured 2D flaky Fe/void/C composites by using α-Fe2O3 hexagonal flakes as the template, followed by the coating of polydopamine (PDA) on the composite surface and calcination under H2/Ar. The volume shrinkage from Fe2O3 to Fe and PDA to carbon led to the formation of several irregular holes in Fe flakes and void space between the Fe cores and carbon cages. The thickness of carbon cages of the composites can be tailored by the simple modulation of the synthetic parameters. As a result of the synergistic effects of multiple chemical components, the shape anisotropy of iron flakes, and unique yolk-shell structures, the optimized sample exhibited excellent microwave absorption properties. With a matching thickness of only 1.6 mm, the strongest reflection loss (RL) was up to -27.80 dB at 14.72 GHz, and the effective absorption bandwidth (EAB, RL < -10 dB) reached 6.40 GHz (11.60-18.00 GHz), which can cover the whole Ku-band. This study provides a novel approach to adjust and balance the permeability and permittivity of 2D magnetic metal flakes, which may promote the practical applications of flaky magnetic metal materials in microwave absorption.

6.
Nanoscale ; 12(36): 18790-18799, 2020 Sep 28.
Article in English | MEDLINE | ID: mdl-32970071

ABSTRACT

Magnetic particle/carbon hybrid structures are promising candidates for high performance microwave absorbing materials with light weight and strong absorption. However, it remains a great challenge to balance the permittivity and permeability to realize impedance matching and further improve their absorption bandwidth. Herein, an effective strategy is designed to fabricate sandwich-like Co15Fe85@C/RGO composites. By introducing RGO sheets in the hybrid structures, the electromagnetic parameters, impedance matching and microwave absorption properties of the final materials can be well controlled. The optimized Co15Fe85@C/RGO composite shows an excellent microwave absorption performance, the strongest reflection loss (RL) of the sample is up to -33.38 dB at 10.72 GHz with a matching thickness of 2.5 mm, and the effective bandwidth (RL < -10 dB) can reach 9.2 GHz (8.64-17.84 GHz). With a single thickness, such a wide absorption band is rarely reported. Their excellent performance can be ascribed to the synergetic effect of the chemical composition and unique sandwich-like structures, which will improve impendence matching and strong microwave attenuation constants of the composites. Our results provide a facile strategy for tuning the electromagnetic parameters and microwave absorption properties of magnetic metal/carbon hybrid structures.

7.
Eur J Drug Metab Pharmacokinet ; 44(5): 611-618, 2019 Oct.
Article in English | MEDLINE | ID: mdl-30825074

ABSTRACT

BACKGROUND AND OBJECTIVES: Myricetin is a flavonoid compound that is abundant in teas, red wine, berries, herbs and vegetables with a variety of pharmacological properties such as antioxidant, anti-inflammatory and anti-cancer effects. Although there are in vitro studies showing that myricetin inhibits human cytochrome P450 (CYP) 2D6 and CYP3A, the inhibitory mechanisms of myricetin on CYP enzymes are still unclear. The aim of this study was to evaluate the inhibitory effects of myricetin on human and rat CYPs, including CYP3A2/3A4, CYP2B1/2B6, CYP2C9/2C11 and CYP2D1/2D6. METHODS: This study was performed to investigate the inhibitory effects of myricetin on human CYP3A4, CYP2B6, CYP2C9, CYP2D6 and rat CYP3A2, CYP2B1, CYP2C11, CYP2D1 through the cocktail approach using ultra-performance liquid chromatography tandem mass spectrometry. Typical probe substrates were used as follows-midazolam for CYP3A2/3A4, dextromethorphan for CYP2D1/2D6, tolbutamide for CYP2C9/2C11, and bupropion for CYP2B1/2B6. RESULTS: The results of this study showed that myricetin might not be a time-dependent inhibitor. Moreover, myricetin inhibited CYP3A4 in an uncompetitive way with an inhibition constant (Ki) value of 143.1 µM. It was also a noncompetitive inhibitor of CYP2C9 and CYP2D6 with Ki values of 31.12 and 53.44 µM and a competitive inhibitor of CYP2B1 with a Ki value of 69.70 µM, as well as a mixed inhibitor of CYP3A2, CYP2C11 and CYP2D1with Ki values of 37.57, 14.88 and 17.39 µM, respectively. CONCLUSIONS: In conclusion, this study indicates that myricetin inhibited CYP3A4/3A2, CYP2C9/2C11, CYP2D6/2D1 and CYP2B1 by various mechanisms with different Ki values. Given that our experiments are established in vitro, further in vivo work is needed to confirm the interaction between myricetin and CYP enzymes, thus providing better guidance for the safe clinical use of myricetin.


Subject(s)
Cytochrome P-450 Enzyme Inhibitors/pharmacology , Cytochrome P-450 Enzyme System/metabolism , Flavonoids/pharmacology , Liver/metabolism , Microsomes, Liver/drug effects , Microsomes, Liver/metabolism , Animals , Chromatography, Liquid/methods , Humans , Rats , Tandem Mass Spectrometry/methods
8.
Drug Dev Ind Pharm ; 45(4): 689-693, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30632818

ABSTRACT

We investigated the effect of azole antifungal drugs (ketoconazole, voriconazole, and itraconazole) on the pharmacokinetics of apatinib in rats. The rats in ketoconazole, voriconazole, and itraconazole groups received single-dose apatinib 30 mg/kg after the oral administration of ketoconazole, voriconazole, and itraconazole, respectively. Co-administration of ketoconazole or voriconazole significantly increased the apatinib Cmax and AUC(0-t) and decreased the clearance. Co-administration of itraconazole did not significantly affect the pharmacokinetics parameters of apatinib. It could be concluded that both ketoconazole and voriconazole significantly increase the exposure of apatinib, and affect the pharmacokinetics of apatinib in rat. Apatinib can be co-administered with itraconazole, but ketoconazole and voriconazole should be avoided if possible or be underwent therapeutic drug monitoring of apatinib. A further clinical study should be conducted to investigate the inhibitory effect of azole antifungal drugs on the apatinib plasma concentration.


Subject(s)
Antifungal Agents/pharmacology , Antineoplastic Agents/pharmacology , Pyridines/pharmacology , Animals , Antineoplastic Agents/therapeutic use , Drug Evaluation, Preclinical , Drug Interactions , Drug Monitoring , Itraconazole/pharmacology , Itraconazole/therapeutic use , Ketoconazole/pharmacology , Ketoconazole/therapeutic use , Male , Mycoses/drug therapy , Pyridines/therapeutic use , Rats , Rats, Sprague-Dawley , Stomach Neoplasms/drug therapy , Voriconazole/pharmacology , Voriconazole/therapeutic use
9.
Drug Dev Ind Pharm ; 45(1): 27-31, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30156133

ABSTRACT

OBJECTIVE: To investigate the impact of resveratrol on the metabolism of ibrutinib in vitro and in vivo. METHODS: In vitro, rat liver microsomes (RLM) and human liver microsomes (HLM) were used to study. In vivo, 18 male SD rats were randomly divided into three groups (n = 6): ibrutinib and the multiple dose of 100 mg/kg resveratrol for consecutive 7 days (Group A), ibrutinib and the single dose of 100 mg/kg resveratrol (Group B), ibrutinib (Group C). Processed samples were analyzed by UPLC-MS/MS. RESULTS: Resveratrol showed inhibition on RLM and HLM in vitro. The IC50 of resveratrol was 8.745 µM in RLM and 7.789 µM in HLM. Furthermore, Groups A and B both increased the AUC and reduced the CLz/F. The Cmax of Group A and the MRT(0-t) of Group B were significantly improved. CONCLUSIONS: Resveratrol inhibits the pharmacokinetic of ibrutinib in vitro and in vivo. It is necessary to pay more attention to adjust the dose of the drug when resveratrol is used in combination with ibrutinib.


Subject(s)
Antioxidants/pharmacokinetics , Pyrazoles/pharmacokinetics , Pyrimidines/pharmacokinetics , Resveratrol/pharmacokinetics , Tandem Mass Spectrometry/methods , Adenine/analogs & derivatives , Animals , Antioxidants/analysis , Chromatography, High Pressure Liquid/methods , Dose-Response Relationship, Drug , Drug Interactions/physiology , Humans , Male , Microsomes, Liver/drug effects , Microsomes, Liver/metabolism , Piperidines , Pyrazoles/analysis , Pyrimidines/analysis , Random Allocation , Rats , Rats, Sprague-Dawley , Resveratrol/analysis
10.
ACS Appl Mater Interfaces ; 10(34): 28839-28849, 2018 Aug 29.
Article in English | MEDLINE | ID: mdl-30079724

ABSTRACT

Due to the increasing demand for military and commercial applications, magnetic metal-based core@shell nanostructures have attracted extensive attention in the field of electromagnetic wave (EMW) absorption materials. To further improve the overall performance, herein, an effective strategy is designed to fabricate Co3Fe7@C yolk-shell structures by using (Co0.9Fe0.1)Fe2O4@phenolic resin core@shell structures as precursors. The structure parameters, including the size of the CoFe alloy cores, the thickness of the carbon shell, and the void between the core and the shell, can be tailored by controlling the reaction conditions. It is demonstrated that the EMW absorption properties of the as-prepared Co3Fe7@C yolk-shell structures are closely related to their structure parameters. The optimized Co3Fe7@C yolk-shell structure shows excellent EMW absorption performance, the strongest reflection loss (RL) is up to -35.3 dB at 9.1 GHz with the matching thickness of 2.0 mm, and the effective bandwidth (RL < -10 dB) can reach 8.4 GHz (9.6-18 GHz) with a thickness of only 1.5 mm. It is revealed that the excellent performances stem from the unique yolk-shell structure as well as the complementarities and synergies between the dielectric loss and the magnetic loss. By rational designing, the magnetic metal alloy@carbon yolk-shell structures will be convinced to have the potential as novel high-efficiency EMW absorption materials with lightweight, low thickness, wide absorption frequency, high stability, and strong absorption characteristics.

11.
Toxicol Lett ; 297: 1-7, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30138636

ABSTRACT

Apatinib, a small molecule anti-angiogenic drug, is proven to be safe and effective for treatment of advanced gastric cancer (AGC). It is also a single drug that significantly prolongs survival after failure of standard chemotherapy for AGC, which has attracted the research interest. The purpose of this study is to evaluate the inhibition effects of apatinib on human and rat cytochrome P450, including CYP3A2/4, CYP2B1/6, CYP2C9/11, CYP2D1/6, and CYP2E1. The IC50 and IC50-shift results indicated that apatinib might not be a time-dependent inhibitor. Apatinib was a weak inhibitor of human CYP2E1 (IC50>10 µM) but inhibited CYP2B6/2B1 and CYP2D6/2D1 in a competitive way (Ki = 3.84/0.59 and 5.41/0.87 µM), and inhibited CYP3A4/3A2 and rat CYP2E1 in a mixed way (Ki = 11.50/1.83 and 13.06 µM). On CYP2C9, apatinb exhibited the noncompetitive inhibition (Ki = 0.71 µM) while it inhibited CYP2C11 uncompetitively (Ki = 3.30 µM).


Subject(s)
Angiogenesis Inhibitors/pharmacology , Cytochrome P-450 Enzyme Inhibitors/pharmacology , Pyridines/pharmacology , Animals , Cytochrome P-450 Enzyme System/metabolism , Drug Interactions , Humans , Isoenzymes/antagonists & inhibitors , Kinetics , Microsomes, Liver/drug effects , Microsomes, Liver/enzymology , Rats
12.
Basic Clin Pharmacol Toxicol ; 123(6): 721-726, 2018 Dec.
Article in English | MEDLINE | ID: mdl-29964362

ABSTRACT

The objective of this study was to evaluate the effect of apatinib on the pharmacokinetics of venlafaxine and O-desmethylvenlafaxine in SD rats and the inhibitory effects of apatinib on venlafaxine in rat and human liver microsomes. Twenty-one SD male rats were randomly divided into three groups (n = 7): group A (multiple dose of 40 mg/kg apatinib for 7 days), group B (single dose of 40 mg/kg apatinib) and group C (the control group). All samples were measured by UPLC-MS/MS. The results indicated that a single dose of apatinib increased the AUC(0-t) , AUC(0-∞) and Cmax of both venlafaxine and O-desmethylvenlafaxine significantly, while Vz/F and CLz/F were decreased. As for group A, only AUC(0-t) and CLz/F of venlafaxine were changed, while no parameters of O-desmethylvenlafaxine were altered. In addition, apatinib was determined to be a mixed inhibitor of venlafaxine.


Subject(s)
Desvenlafaxine Succinate/pharmacokinetics , Protein Kinase Inhibitors/pharmacology , Pyridines/pharmacology , Venlafaxine Hydrochloride/pharmacokinetics , Animals , Chromatography, High Pressure Liquid , Desvenlafaxine Succinate/blood , Drug Interactions , Humans , Inhibitory Concentration 50 , Male , Mass Spectrometry , Microsomes, Liver/drug effects , Rats , Rats, Sprague-Dawley , Venlafaxine Hydrochloride/blood
13.
Luminescence ; 33(2): 312-317, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29058364

ABSTRACT

A series of Bi3+ ,Eu3+ -doped BaMoO4 phosphors was synthesized using a hydrothermal method. The crystal structure, morphology and optical properties of the phosphors were studied using X-ray diffraction (XRD), scanning electron microscope (SEM) and photoluminescence (PL) measurements. Three different particle morphologies were detected in the SEM observation. The energy dispersive spectroscopy (EDS) results indicated that the solubility of Bi3+ in spherical or rugby-like BaMoO4 particles was very low and the excess Bi3+ element was cumulated in the irregular particles. Characteristic emissions of Eu3+ ions (5 D0  â†’ 7 FJ ; J = 0, 1, 2, 3, 4) were observed under excitation in ultraviolet (UV) light, with the most intense transition being the 5 D0  â†’ 7 F2 transition. Energy transfer from MoO42- and Bi3+ to Eu3+ can be readily achieved. Red emission intensity of Eu3+ was enhanced by a factor of two by co-doping with a small amount of Bi3+ . Optical properties as a function of Bi3+ content were studied and the optimum Bi3+ content in BaMoO4 nanocrystals was determined to be 0.4 mol%.


Subject(s)
Barium/chemistry , Bismuth/chemistry , Europium/chemistry , Luminescent Agents/chemistry , Energy Transfer , Luminescent Agents/chemical synthesis , Luminescent Measurements , X-Ray Diffraction
14.
Drug Des Devel Ther ; 11: 3503-3510, 2017.
Article in English | MEDLINE | ID: mdl-29263648

ABSTRACT

AIM: Human cytochrome P450 3A4 is the most abundant isoform of P450 enzyme in the liver. It plays an important role in the metabolism of wide variety of xenobiotic and endogenous substrates. So far, there are few reports about the functional characterization of CYP3A4 variants in terms of specific substrates. The aim of this study was to systematically investigate the genetic polymorphisms of 23 CYP3A4 alleles and evaluate their catalytic activities on the metabolism of lidocaine in vitro. METHODS AND RESULTS: The wild-type and 22 CYP3A4 variants were expressed in Spodoptera frugiperda 21 insect cells. Then the insect microsomes were incubated with the CYP3A4-specific substrate lidocaine. Reactions were performed with 50-3,000 µM for 60 min at 37°C. Lidocaine and its metabolite monoethylglycinexylidide were analyzed by ultra-performance liquid chromatography-tandem mass spectrometry system. Of the 23 CYP3A4 allelic variants tested, 2 variants (CYP3A4*17 and CYP3A4*30) had no detectable enzyme activity; and 5 variants (CYP3A4*2, CYP3A4*5, CYP3A4*9, CYP3A4*16 and CYP3A4*24) showed significantly decreased intrinsic clearance values compared with wild-type CYP3A4*1. CONCLUSION: As the first study of all these CYP3A4 alleles for lidocaine metabolism, our results in vitro assessment may provide novel insights into the allele-specific and substrate-specific activity of CYP3A4 and may also offer a reference to the personalized treatment of lidocaine in a clinical setting.


Subject(s)
Alleles , Cytochrome P-450 CYP3A/genetics , Cytochrome P-450 CYP3A/metabolism , Genetic Variation/genetics , Lidocaine/metabolism , Animals , Humans , Microsomes/enzymology , Microsomes/metabolism , Spodoptera/cytology
15.
J Chromatogr B Analyt Technol Biomed Life Sci ; 1068-1069: 84-89, 2017 Nov 15.
Article in English | MEDLINE | ID: mdl-29032042

ABSTRACT

Brigatinib is the second-generation anaplastic lymphoma kinase - inhibitor in non-small cell lung cancer and it can overcome the crizotinib-resistance. Chromatographic separation was carried out on an Acquity Ultra Performance Liquid Chromatography (UPLC) unit with a BEH C18 column (2.1mm×50mm, 1.7µm). The mobile phase was composed of acetonitrile and 0.1% formic acid in water. No endogenous interfering compounds was discovered at retention time of brigatinib (0.56min) and imatinib (IS, 1.41min). MS/MS detection was performed in positive mode. And the MRM transitions were m/z 584.09→484.08 and m/z 494.3→394.2 for brigatinib and IS, respectively. This method was assessed to be stable, specificity, and no matrix effect in three concentrations (0.004, 0.4, 4µg/mL). The intra-day and inter-day precisions were less than 11.09% and 6.43%. And intra-day and inter-day accuracies were ranged from -3.88% to 5.44%. The recovery of brigatinib was from 85.26% to 96.05%. Additionally, the method had a good linearity in the range of 0.002-5µg/mL. The presented method was effectively implemented to determine the concentration of brigatinib in rat plasma.


Subject(s)
Chromatography, High Pressure Liquid/methods , Organophosphorus Compounds/blood , Organophosphorus Compounds/pharmacokinetics , Pyrimidines/blood , Pyrimidines/pharmacokinetics , Tandem Mass Spectrometry/methods , Animals , Drug Stability , Limit of Detection , Linear Models , Male , Organophosphorus Compounds/chemistry , Pyrimidines/chemistry , Rats , Rats, Sprague-Dawley , Reproducibility of Results
16.
J Pharmacol Sci ; 135(1): 8-13, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28927781

ABSTRACT

BACKGROUND: Cytochrome P450 proteins (CYP 450) is the most important enzyme system of drug phase I metabolism in liver. In previous reports, reduced efficiency or increased risk of adverse events can be affected by primary sequence mutation in CYP450. AIM: To investigate the effect of gene polymorphism on the metabolism of ketamine in vitro, including the new alleles: 2C9*58, *59 and *60. METHOD: Incubation system which was contained insect microsome, b5, NADPH and 1M PBS incubated 10 µM-1000 µM ketamine in 37 °C for 40 min concentration of norketamine was analyzed by ultra-performance liquid chromatography-tandem mass spectrometry system (UPLC-MS/MS). RESULT: Catalytic activity of thirty-eight CYP2C9 alleles on ketamine metabolism to norketamine was surveyed. Compared with 2C9*1, three alleles (2C9*40, *49 and *51) was demonstrated dramatically increased intrinsic clearance (1.2-fold-3.75-fold); four subtypes (2C9*27, *31, *41 and *56) exhibited no significantly change on enzyme activity. The resting 31 alleles expressed different degrees of reduction compared with wild type. CONCLUSION: The result of research warns that attention should be more paid on individual who carry on the special 2C9 alleles under the situation of administrating ketamine.


Subject(s)
Cytochrome P-450 CYP2C9/genetics , Cytochrome P-450 CYP2C9/physiology , Ketamine/metabolism , Pharmacogenomic Variants/genetics , Pharmacogenomic Variants/physiology , Polymorphism, Genetic/genetics , Polymorphism, Genetic/physiology , Animals , Sf9 Cells
17.
Hepatogastroenterology ; 61(134): 1556-62, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25436342

ABSTRACT

BACKGROUND: Treatment of complicated hepatolithiasis is complex and difficult. In this report, we present a novel approach to manage complicated hepatolithiasis using the rigid choledochoscope guided by CT-based 3D reconstruction technique with or without hepatectomy. METHODS: Between February 2012 to December 2013, 25 patients with complicated hepatolithiasis underwent rigid choledochoscope guided by CT-based 3D reconstruction technique combined with or without hepatectomy. 27 patients with complicated hepatolithiasis underwent a traditional operation (traditional method group) from June 2011 to January 2012. All operations were performed by the authors. RESULTS: The final stone clearance rate of the rigid choledochoscope group was 96%, whereas that of the traditional method group was 74.1% (P=0.032). There was no patient died of postoperative mortality in two groups. Moreover, the operative time in the traditional method group was significantly longer than that in the rigid choledochoscope group (P=0.010). Recurrent intrahepatic bile duct stones were not found during the follow-up period in the two groups. CONCLUSIONS: Operative rigid choledochoscope guided by CT-based 3D reconstruction technique combined with or without hepatectomy may be an effective and safe treatment for complicated hepatolithiasis.


Subject(s)
Cholelithiasis/surgery , Endoscopes , Endoscopy , Imaging, Three-Dimensional , Liver Diseases/surgery , Radiographic Image Interpretation, Computer-Assisted , Radiography, Interventional/methods , Surgery, Computer-Assisted , Tomography, X-Ray Computed , Adult , Aged , Cholelithiasis/complications , Cholelithiasis/diagnostic imaging , Endoscopy/instrumentation , Endoscopy/methods , Equipment Design , Female , Hepatectomy , Humans , Liver Diseases/complications , Liver Diseases/diagnostic imaging , Male , Middle Aged , Operative Time , Predictive Value of Tests , Retrospective Studies , Surgery, Computer-Assisted/instrumentation , Surgery, Computer-Assisted/methods , Time Factors , Treatment Outcome
18.
Nan Fang Yi Ke Da Xue Xue Bao ; 34(7): 945-9, 2014 Jun.
Article in Chinese | MEDLINE | ID: mdl-25057061

ABSTRACT

OBJECTIVE: To construct a three-dimensional (3D) model of arteries supplying the extrahepatic bile duct with a new segmentation algorithm based on submillimeter CT data. METHODS: The new image segmentation algorithm based on interactive volume rendering was integrated into Medical Image Three-Dimensional Visualization System (MI-3DVS) as an intersected plug-in. The abdominal submillimeter CTA data of 10 patients were imported into MI-3DVS and the 3D model of the extrahepatic bile duct and its supplying arteries were constructed. The 3D model was zoomed in, zoomed out and spinned for observation and analysis of the arteries supplying the extrahepatic bile duct. RESULTS: The 3D models of the blood supply to extrahepatic bile duct allowed stereoscopic, and accurate display of the fourth- and fifth-level branches of the hepatic artery, the second-level branches of the cystic artery, the pancreatic duodenal artery arch and the retroportal artery. The 3D models also provided a clear vision of the biliary structures including the hepatobiliary tract, the left and right hepatic ducts, gallbladder, the liver duct, and the common bile duct. CONCLUSION: Based on the segmentation method of interactive volume rendering, the CT data of the arterioles supplying the extrahepatic bile duct can be extracted and segmented for 3D reconstruction to display the three-dimensional anatomical structures of the extrahepatic bile duct and its supplying arteries.


Subject(s)
Bile Ducts, Extrahepatic/anatomy & histology , Hepatic Artery/anatomy & histology , Imaging, Three-Dimensional , Models, Anatomic , Humans , Liver/blood supply
19.
Zhonghua Wai Ke Za Zhi ; 52(1): 55-9, 2014 Jan.
Article in Chinese | MEDLINE | ID: mdl-24697942

ABSTRACT

OBJECTIVE: To explore the application value of the MI-3DVS in patients with hepatic artery variation receiving duodenopancreatectomy. METHODS: A total of 114 patients who had undergone pancreatoduodenectomy were retrospectively summarized and analyzed during January 2010 to July 2012. The clinical data of 64-slice multidetector CT angiography (64-MDCTA) scanning was introduced into MI-3DVS for procedural segmentation, registration and 3-dimensional reconstruction. Based on the reconstructed 3-dimensional model, the origination and bifurcations of variant hepatic artery was observed. And its anatomical relationships with abdominal organs and vessels were also observed. Thereafter, preoperative procedures planning was formulated. The findings were compared to those found during the operation and by postoperative digital subtraction angiography (DSA) of coeliac artery. RESULTS: The abdominal 3D models can clearly display the size and shape of tumor, the origin and course of the blood vessels, as well as the 3D anatomic relationship between tumors and organs, blood vessels. A total of 14 cases (12.3%, 14/114) were found with variant, including 9 cases (7.9%) with replaced right hepatic artery arising from superior mesenteric artery, 3 cases (2.6%) with replaced common hepatic artery arising from superior mesenteric artery, 2 cases (1.8%) with replaced left hepatic artery arising from left gastric artery. The 14 patients all received standard procedures of duodenopancreatectomy. Compared to the intraoperative findings and postoperative DSA examination, the sensitivity, specificity and accuracy of MI-3DVS to variant hepatic artery is 100%. The preoperative planning guided by MI-3DVS is in line with the intraoperative findings.No postoperative complications occurred in all 14 patients, including hepatic abscesses, biliary fistula and liver failure. CONCLUSIONS: MI-3DVS can accurately diagnose hepatic artery variation before duodenopancreatectomy. Therefore, it contributes to the formulation of preoperative surgical plans.It also increases the success rate of the surgical operations and decreases the occurrence of postoperative complications.


Subject(s)
Hepatic Artery/abnormalities , Imaging, Three-Dimensional , Pancreaticoduodenectomy/instrumentation , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Retrospective Studies , Tomography, Spiral Computed , Young Adult
20.
Int J Med Robot ; 10(4): 410-7, 2014 Dec.
Article in English | MEDLINE | ID: mdl-24711375

ABSTRACT

BACKGROUND: Our main aim was to evaluate the value of medical image three-dimensional visualization system (MI-3DVS) in pancreaticoduodenctomy patients with hepatic artery variance. METHODS: 114 patients who had undergone pancreatoduodenectomy were retrospectively summarized and analyzed. Clinical data of 64-slice multidetector CT angiography (64-MDCTA) scanning was introduced into MI-3DVS for procedural segmentation, registration and 3-dimensional (3D) reconstruction. The findings were compared with those found during the operation and by postoperative digital subtraction angiography (DSA) of coeliac artery. RESULTS: The 3D model demonstrated the origination and bifurcations of blood vessels, and the relationships among neoplasms, organs and blood vessels efficiently. About (14/114 cases, 12.3%) had variant. The sensitivity, specificity and accuracy of MI-3DVS in variant hepatic artery diagnosis were 100%. It assisted in preoperative procedural planning that was consistent with intraoperative findings. CONCLUSIONS: MI-3DVS can be applied for accurate diagnosis of hepatic artery variance. It also provides detailed preoperative guidance for individualized procedural planning.


Subject(s)
Hepatic Artery/diagnostic imaging , Imaging, Three-Dimensional/methods , Pancreatic Neoplasms/surgery , Pancreaticoduodenectomy/methods , Adult , Aged , Aged, 80 and over , Angiography, Digital Subtraction , Female , Humans , Male , Middle Aged , Multidetector Computed Tomography , Retrospective Studies
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