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AIMS: A lot of medication risks related to high-dose methotrexate (HDMTX) therapy still remain to be identified and standardized. This study aims to establish an evidence-based practice guideline for individualized medication of HDMTX. METHODS: The practice guideline was launched by the Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society. The guideline was developed following the WHO handbook for guideline development and the methodology of evidence-based medicine (EBM). The guideline was initially registered in the International Practice Guidelines Registry Platform (IPGRP-2017CN021). Systematic reviews were conducted to synthesize available evidence. A multicentre cross-sectional study was conducted using questionnaires to evaluate patients' perception and willingness concerning individualized medication of HDMTX. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to rate the quality of evidence and to grade the strength of recommendations. RESULTS: Multidisciplinary working groups were included in this guideline, including clinicians, pharmacists, methodologists, pharmacologists and pharmacoeconomic specialists. A total of 124 patients were involved to integrate patient values and preferences. Finally, the guideline presents 28 recommendations, regarding evaluation prior to administration (renal function, liver function, pleural effusion, comedications, genetic testing), pre-treatment and routine dosing regimen, therapeutic drug monitoring (necessity, method, timing, target concentration), leucovorin rescue (initial timing, dosage regimen and optimization), and management of toxicities. Of these, 12 are strong recommendations. CONCLUSIONS: We developed an evidence-based practice guideline with respect to HDMTX medication using a rigorous and multidisciplinary approach. This guideline provides comprehensive and practical recommendations involving the whole process of HDMTX administration to health care providers.
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Monitoramento de Medicamentos , Metotrexato , China , Estudos Transversais , Medicina Baseada em Evidências/métodos , Humanos , Metotrexato/efeitos adversosRESUMO
BACKGROUND: Paraquat and diquat are widely used in agricultural production in many countries, which are very toxic to human beings. Paraquat can be detected in some diquat solution sold in the market. The blood concentration of paraquat or diquat is an important indicator for clinical diagnosis of paraquat or diquat poisoning. So, it is very meaningful to develop a method for simultaneous determination of paraquat and diquat in human plasma. OBJECTIVE: To develop and validate a HPLC-DAD method for simultaneous determination of paraquat and diquat in human plasma and to apply it in the acute poisoning patients by these two herbicides. METHODS: Paraquat and diquat were simultaneously determined by HPLC-DAD. The plasma was treated using Waters OASIS® Column and then separated on a Thermo Hypersil GOLD (250 × 4.6 mm, 5 µm) Column with the mobile phase consisted of 75 mmol/L sodium heptane sulfonate (containing 0.1 mol/L phosphoric acid, pH 3.0) and acetonitrile (87:13, v:v) at a flow rate of 1.0 mL/min. The full-wavelength scanning was 200-400 nm, and the detection wavelength of paraquat and diquat was 257nm and 310nm, respectively. 120 and 30 plasma samples from patients with paraquat and diquat poisoning were collected and analyzed by the established method. RESULTS: The standard curve for paraquat and diquat ranged from 0.05 to 20 µg/mL, and the precision of LLOQ for paraquat was 16.49%, which was required to be less than 20%. The precision of other concentrations was less than 14.14%. The recovery of paraquat and diquat was 95.38%-103.97% and 94.79%-98.40%, respectively. The results showed that paraquat and diquat were stable under various storage conditions. 120 plasma samples of paraquat poisoning patients and 30 plasma samples of diquat poisoning patients were determined by the established method. The blood concentration of paraquat ranged from 0.10 to 20.62 µg/mL, with an average of 3.61 µg/mL, while for diquat, the concentration ranged from 0 to 26.59 µg/mL, with an average of 2.00 µg/mL. Among the diquat suspected poisoning samples, 5 samples were detected not only diquat but also paraquat, and 2 samples were detected only paraquat, no diquat. CONCLUSION: The HPLC-DAD method established in this study was high throughput, high sensitivity, simple operation, and wide linear ranges. It can be used for the screening analysis and quantitative detection of paraquat and diquat in acute poisoning patients, which can provide basis for the treatment and prognosis of these two herbicides poisoning patients.
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Cromatografia Líquida de Alta Pressão/métodos , Diquat/sangue , Paraquat/sangue , Intoxicação/sangue , Calibragem , Cromatografia Líquida de Alta Pressão/instrumentação , Diquat/intoxicação , Herbicidas/sangue , Herbicidas/intoxicação , Humanos , Limite de Detecção , Paraquat/intoxicação , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Clinical practice guidelines or recommendations often require timely and regular updating as new evidence emerges, because this can alter the risk-benefit trade-off. The scientific process of developing and updating guidelines accompanied by adequate implementation can improve outcomes. To promote better management of patients receiving vancomycin therapy, we updated the guideline for the therapeutic drug monitoring (TDM) of vancomycin published in 2015. METHODS: Our updated recommendations complied with standards for developing trustworthy guidelines, including timeliness and rigor of the updating process, as well as the use of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. We also followed the methodology handbook published by the National Institute for Health and Clinical Excellence and the Spanish National Health System. RESULTS: We partially updated the 2015 guideline. Apart from adults, the updated guideline also focuses on pediatric patients and neonates requiring intravenous vancomycin therapy. The guideline recommendations involve a broadened range of patients requiring TDM, modified index of TDM (both 24-hour area under the curve and trough concentration), addition regarding the necessity and timing of repeated TDM, and initial dose for specific subpopulations. Overall, 1 recommendation was deleted and 3 recommendations were modified. Eleven new recommendations were added, and no recommendation was made for 2 clinical questions. CONCLUSIONS: We updated an evidence-based guideline regarding the TDM of vancomycin using a rigorous and multidisciplinary approach. The updated guideline provides more comprehensive recommendations to inform rational and optimized vancomycin use and is thus of greater applicability.
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Monitoramento de Medicamentos , Vancomicina , Adulto , Povo Asiático , Criança , China , Humanos , Recém-Nascido , Sociedades , Vancomicina/uso terapêuticoRESUMO
Bi metal attached BiOBr with oxygen defect (BiOBr(3)-Bi(x%, x = 10, 20, 30)) nanosheets was prepared via the hydrothermal process in this study. The different characterization techniques of x-ray diffraction, x-ray photoelectron spectrometer, electron spin resonance (ESR), field emission scanning electron microscope, and high resolution transmission electron microscope were used to distinguish the composition, crystal structure, and morphology of the samples. Under visible light irradiation, the BiOBr(3)-Bi(x%, x = 10, 20, 30) samples exhibited improved photocatalytic activity for the degradation of colored dyes (RhB) and colorless tetracycline hydrochloride. Such an improvement was ascribed to the widened visible light absorption and enhanced separation of the photogenerated electron-hole pairs because of the synergistic effect of oxygen vacancies and Bi metal with plasmon resonance effects. A possible photocatalytic mechanism of the quasi Z-scheme process was proposed on the basis of ESR measurements and radical-trapping experiments.
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The aim of this study was to characterize the serum metabolic profiles of patients with Alzheimer's disease (AD) and amnestic mild cognitive impairment (AMCI) using metabolomics based on gas chromatography-mass spectrometry (GC/MS). Serum samples were collected from patients with AD (n = 30) and AMCI (n = 32), and normal healthy controls (NOR, n = 40). Metabolite profiles were performed with GC/MS in conjunction with multivariate statistical analysis, and possible biomarker metabolites were identified. Thirty-one kinds of endogenous metabolites could be identified simultaneously. Eleven components were chosen as biomarker metabolites between AD and NOR groups, and these metabolites were closely related to seven biological pathways: arginine and proline metabolism, phenylalanine metabolism, ß-alanine metabolism, primary bile acid synthesis, glutathione metabolism, starch and sucrose metabolism, and steroid hormone biosynthesis. Meanwhile, 10 components were chosen as biomarker metabolites between AMCI and NOR groups and seven biological pathways were closely related: arginine and proline metabolism, phenylalanine metabolism, citrate cycle, alanine, aspartate and glutamate metabolism, taurine and hypotaurine metabolism, starch and sucrose metabolism, and steroid hormone biosynthesis. Our study distinguished serum metabotypes between AD, AMCI and NOR patients successfully. The implementation of this metabolomic strategy may help to develop biochemical insight into the metabolic alterations in AD/AMCI and will be helpful for the further understanding of pathogenesis.
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Doença de Alzheimer , Disfunção Cognitiva , Cromatografia Gasosa-Espectrometria de Massas/métodos , Metabolômica/métodos , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/sangue , Doença de Alzheimer/metabolismo , Biomarcadores/sangue , Disfunção Cognitiva/sangue , Disfunção Cognitiva/metabolismo , Feminino , Humanos , Masculino , Metaboloma , Pessoa de Meia-Idade , Análise de Componente PrincipalRESUMO
Currently beraprost sodium (BPS) is widely proposed to ameliorate the symptoms caused by chronic arterial occlusive disease. The objective of this study is to investigate the BPS pharmacokinetic characteristics, its vasodilating effect and the relationship between plasma concentration vs response effect. 12 healthy Chinese volunteers (6 male, 6 female) were chosen to participate in a single center, random, and open design study. After overnight fasting, BPS (dose = 40µg) was administrated orally to each volunteer. The blood samples were collected at different time points (from 0 to 5 h after administration) and BPS concentration was analyzed by LC-MS/MS method. The vasodilating effect was evaluated by detecting the skin microcirculation blood flow of volunteers' fingers with laser Doppler fluxmetry. The Cmax of BPS was (601.14 ± 214.81) pg/mL, the Tmax was (0.58 ± 0.48) h, and AUC0-t was (1020.41±214.63) pg/mLâ¢h. BPS exhibited significant vasodilating effect since the skin microcirculation blood flow increased definitely at 0.25, 0.5, and 0.75 h (all p<0.05) after drug administration, and a positive correlation was presented between the pharmacokinetics and the vasodilating effect, which would be beneficial for guiding BPS dosage in clinical.
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Epoprostenol/análogos & derivados , Vasodilatadores/farmacocinética , Adulto , Área Sob a Curva , Cromatografia Líquida/métodos , Epoprostenol/farmacocinética , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pele/metabolismo , Espectrometria de Massas em Tandem/métodos , Equivalência Terapêutica , Adulto JovemRESUMO
BACKGROUND: Therapeutic drug monitoring of vancomycin is very valuable due to the good correlation between trough levels and clinical outcome. Therefore, it is important to accurately determine the concentration of vancomycin in patient plasma for adequate dose-adjustment. The objective of this study was to develop a new liquid chromatography-mass spectrometry (LC-MS) method for determination of vancomycin in patient plasma and compare the results with those obtained from enzyme-multiplied immunoassay technique (EMIT). METHODS: After extraction by simple protein precipitation, vancomycin and bergenin (internal standard) were separated on a C18 column (150×4.6 mm, 5 µm) at 40°C by gradient elution with 0.1% formic acid and acetonitrile as the mobile phase and measured by electrospray ionization source in positive selective ion monitoring mode. Seventy-nine plasma samples from patients with severe infection were analyzed by enzyme-multiplied immunoassay technique and LC-MS method. MedCalc 15.2 software with Bland-Altman analysis and Passing-Bablok regression analysis was used for statistical analysis. RESULTS: The weighted (1/x2) calibration curve of the validated LC-MS was linear within the concentration range of 0.25 - 40 µg/mL. The inter- and intra-day precisions (%RSD) were less than 10.0%. No significant matrix effect was observed in the relevant time ranges. Comparison of the two methods indicated that results of the LC-MS were close to that of EMIT with a correlation coefficient of 0.957. Upon Bland-Altman analysis, the bias amounted to 2.9 µg/mL (95% confidence intervals of -3.4 - 9.2 µg/mL). CONCLUSIONS: The established LC-MS method and EMIT were both suitable for routine TDM of vancomycin.
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Cromatografia Líquida/métodos , Monitoramento de Medicamentos/métodos , Imunoensaio/métodos , Infecções/sangue , Espectrometria de Massas/métodos , Vancomicina/sangue , Antibacterianos/sangue , Antibacterianos/farmacocinética , Antibacterianos/uso terapêutico , Povo Asiático , China , Humanos , Infecções/tratamento farmacológico , Infecções/etnologia , Reprodutibilidade dos Testes , Vancomicina/farmacocinética , Vancomicina/uso terapêuticoRESUMO
BACKGROUND: Tetramethylpyrazine, isolated from Ligusticum wallichii Franch., is widely used for the treatment of cerebrovascular and cardiovascular diseases in China. OBJECTIVE: To assess and compare the pharmacokinetic characteristics and bioequivalence of two tetramethylpyrazine phosphate (TMPP) tablets in healthy Chinese male subjects. MATERIALS AND METHODS: 20 healthy male subjects were randomly divided into two groups according to a two-period crossover design test. A single oral dose of 200 mg test or reference tablets was given with a 7-day washout period under fasting conditions. Blood samples were taken at scheduled time points, and the concentration of TMPP was measured by LC-MS. Drug And Statistical Software-Version 2.0 was used to calculate the pharmacokinetic parameters and assess bioequivalence of the two formulations. RESULTS: 20 subjects were enrolled in the study, and none dropped out. The main pharmacokinetic parameters of test and reference formulations were as follows: T1/2 was (1.79 ± 0.82) hours and (1.64 ± 0.52) hours, tmax was (0.76 ± 0.37) hours and (0.94 ± 0.44) hours, Cmax was (961.14 ± 309.64) ng/mL and (1,059.09 ± 350.69) ng/mL, AUC0-12h was (1,744.69 ± 643.49) ng×h/mL and (1,726.32 ± 494.11) ng×h/mL, AUC0-∞ was (1,756.95 ± 643.63) ng×h/mL and (1,740.16 ± 504.89) ng×h/mL, respectively. The relative bioavailability of TMPP tablets was 102.4 ± 26.0%, and no serious adverse events were reported. CONCLUSION: This single-dose study in healthy Chinese male fasted subjects showed that the TMPP test and reference tablets were bioequivalent.â©.
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Extratos Vegetais/farmacocinética , Pirazinas/farmacocinética , Adolescente , Adulto , Área Sob a Curva , Povo Asiático , Disponibilidade Biológica , Estudos Cross-Over , Meia-Vida , Voluntários Saudáveis , Humanos , Masculino , Extratos Vegetais/administração & dosagem , Pirazinas/administração & dosagem , Pirazinas/efeitos adversos , Comprimidos , Equivalência Terapêutica , Adulto JovemRESUMO
Brusatol, a quassinoid isolated from the traditional Chinese medicine Brucea javanica, has been reported to be an inhibitor of Nrf2 pathway and has great potential to be developed into a novel chemotherapeutic adjuvant. However, the in vivo process of brusatol has not been comprehensively explained yet. Therefore, this paper focused on the pharmacokinetic metabolism and excretion of brusatol in rats using a simple and reproducible LC-MS/MS method. The results indicated that the plasma concentration of brusatol decreased rapidly; the average cumulative excretion rate in urine was 5.82% during 24 h, and 0.71% in bile during 12 h. High-resolution mass spectrometry was applied for the identification of metabolites; as a result, four metabolites were detected and the structure was tentatively deduced on the base of the MS2 data, Compound Discoverer 2.0 and Mass Frontier 7.0 software. Hydroxylation, hydrolysis and glucuronidation were suggested as major metabolic pathways in vivo. The in vivo process and detection of metabolites of brusatol might improve the understanding of the mechanism of its anticancer effect and provide valuable information for its safety estimation, which will be essential to the new drug development.
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Metabolômica/métodos , Quassinas/análise , Quassinas/farmacocinética , Animais , Fezes/química , Limite de Detecção , Modelos Lineares , Masculino , Metaboloma , Quassinas/metabolismo , Ratos , Ratos Wistar , Reprodutibilidade dos TestesRESUMO
The narrow therapeutic index, non-linear pharmacokinetics and unpredictable absorption require regular therapeutic monitoring of phenytoin. The influence of genetic differences, sex, age and race on the phenytoin plasma levels and its metabolites is well recognized. This study is aimed at evaluating phenytoin plasma drug concentration and its relationship with clinical response, persistent seizures and toxicity in different gender and various age groups of Chinese epileptic patients. This knowledge will help the clinicians in adjusting the drug dosages of phenytoin in various sub-groups of epileptic patients for enhancing the safety, efficacy and minimizing the toxicity of phenytoin. A total of 48 plasma samples of epileptic patients for measuring the plasma phenytoin concentration were received. Only patients displaying persistent seizures or suspected of adverse effects were requested for drug monitoring. All these samples were analyzed for therapeutic drug monitoring with Enzyme-multiplied immunoassay technique. Surprisingly, it was found that majorities (85.5%) of samples were out of the reference range, of which 69% of samples were in sub-therapeutic levels and 16.5% of samples were above therapeutic levels. Only 14.5% of all samples had phenytoin levels in the therapeutic range. The difference in plasma concentration of phenytoin was notably altered in gender and various age groups. Careful attention must be applied to specific gender and particular age group on an individual basis in the interpretation of plasma concentration results, in order to facilitate the modification of doses and develop the best approach in treatment and to obtain the desired clinical response because multiple factors can affect the phenytoin plasma concentration. Through these results, it can be concluded that a good correlation exists between phenytoin plasma concentration and clinical response. Therefore, regular therapeutic monitoring of phenytoin and screening of HLA-A, B, C and DRB1 genotypes before prescribing phenytoin in epileptic patients is essentially required to achieve maximum clinical response and prevent the serious toxicity.
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Monitoramento de Medicamentos/estatística & dados numéricos , Fenitoína/farmacocinética , Fenitoína/uso terapêutico , Convulsões/tratamento farmacológico , Adulto , Fatores Etários , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/sangue , Anticonvulsivantes/farmacocinética , Anticonvulsivantes/uso terapêutico , Criança , Feminino , Humanos , Masculino , Fenitoína/efeitos adversos , Fenitoína/sangue , Convulsões/sangue , Fatores SexuaisRESUMO
The unpredictable and unfavorable connection of dose and plasma concentration of valproic acid supports the necessity to regularly measure its plasma concentration. The present study is drug monitoring of valproic acid and comparative evaluation of therapeutic monitoring results of valproic acid for assessment of clinical response, safety and toxicity in different age and gender groups of Chinese epileptic patients. This knowledge will help the clinicians in adjusting the drug dosages of valproic acid in various sub-groups of epileptic patients for enhancing the safety and minimizing the toxicity of valproic acid. A total of 206 plasma samples (126 males and 80 females) of epileptic patients using valproic acid were requested for therapeutic drug monitoring by neurology department of Qilu Hospital. It was found that 29 % of the total samples were found in sub-therapeutic levels, 13% of the samples had toxic levels and 58% of all the samples had valproic acid levels in therapeutic range. The difference in plasma concentration of valproic acid is notably altered in gender and various age groups. However, this requires further investigation. Despite the majority of samples in the therapeutic range, there was an unfavorable clinical response. The outcomes of the current research work exposed that there was a poor correlation between the plasma concentration and clinical response. Careful attention must be applied to specific gender and particular age group on an individual basis in the interpretation of plasma concentration results, in order to facilitate the modification of doses and develop the best approach in treatment and to obtain the desired clinical response because multiple factors can affect the valproic acid plasma concentration. Through these results, it can be concluded that poor correlation exists between valproic acid plasma concentration and clinical response.
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Monitoramento de Medicamentos/estatística & dados numéricos , Ácido Valproico/farmacocinética , Adulto , Fatores Etários , Idoso , Anticonvulsivantes/sangue , Anticonvulsivantes/farmacocinética , Anticonvulsivantes/uso terapêutico , Pré-Escolar , Epilepsia/tratamento farmacológico , Feminino , Humanos , Lactente , Masculino , Fatores Sexuais , Resultado do Tratamento , Ácido Valproico/sangue , Ácido Valproico/uso terapêuticoRESUMO
Epirubicin is widely used for the therapy of various breast cancers. However, it has serious adverse side effects, particularly cardiotoxicity, which can cause irreversible damage in patients. Paeonol, an active component from Moutan Cortex, enhances antitumor activity of antineoplastics and reduces toxicities induced by chemotherapeutics. In this study, we investigated the anticancer activity of Paeonol in combination with Epirubicin against breast cancer and the alleviated effect of Paeonol on cardiotoxicity induced by Epirubicin. The apoptosis results and the coefficient of drug interaction values suggested significantly synergistic in combination of Paeonol and Epirubicin to 4T1 and MCF-7 cells. We further examined antitumor activities of Paeonol or/and Epirubicin in vivo in BALB/c mice and found that co-treatment of Paeonol and Epirubicin had a synergistic inhibitory effect on tumor growth and enhanced apoptosis in tumors in vivo compared with Epirubicin alone. Increased apoptosis was associated with the activation of apoptosis-related proteins including PARP, Bax, caspase 3, and inhibition of p38/JNK/ERK MAPKs. Moreover, Paeonol exhibited a mitigative effect on Epirubicin-induced cardiotoxicity through suppressing NF-kB pathway. In conclusion, Paeonol (a) enhanced the antitumor activity of Epirubicin in a synergistic manner against breast cancer cells via inhibiting p38/JNK/ERK MAPKs and (b) alleviated Epirubicin-induced cardiotoxicity by suppressing NF-kB pathway. These findings suggest that combination of Paeonol and Epirubicin is potentially applicable for breast cancer treatment.
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Acetofenonas/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias da Mama/tratamento farmacológico , Epirubicina/farmacologia , Neoplasias Mamárias Experimentais/tratamento farmacológico , Acetofenonas/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Western Blotting , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Cardiotoxicidade/etiologia , Cardiotoxicidade/prevenção & controle , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sinergismo Farmacológico , Epirubicina/administração & dosagem , Epirubicina/efeitos adversos , Feminino , Humanos , Imuno-Histoquímica , Células MCF-7 , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Camundongos Endogâmicos BALB C , Microscopia de Fluorescência , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Carga Tumoral/efeitos dos fármacosRESUMO
Spikes in Lamotrigine concentrations levels and associated clinical toxicity may occur unpredictably. This study describes the development and validation of a simple, more rapid, highly sensitive and economical method for measuring Lamotrigine (LTG) concentration levels in human plasma using HPLC-UV and its clinical applications. Analyte from plasma was extracted with methanol (protein precipitation) and separated on the analytical column Diamonsil C18 (150mm×4.6mm, 5µm) Waters-Milford, MA, United States. Mixture of 0.1% Trifluoroacetate and Methanol used as mobile phase in a 59:41 volume/volume mixture with an isocratic flow rate of 1.5 ml/min and wavelength was adjusted to 260nm. Standard curve of lamotrigine showed good linearity over the range of 1.0-50µg/mL (r2=0.9961) and LLOQ was 1.0µg/ml. The Specificity, Recovery, Accuracy, Stability, Robustness and RSDs for both intraday and interday precision were within acceptable limits. The highly sensitive HPLC assay for determination of LTG in human plasma was demonstrated, validated and applied in Therapeutic Drug Monitoring (TDM) of sixty seven epilepsy patients who were using LTG. The proposed method can be easily applied in routine Therapeutic monitoring of LTG, Besides TDM, stated method can be also very useful for Bioequivalence studies, Pharmacovigilance and Pharmacokinetics studies.
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Glucuronidation plays critical role in the elimination of bergenin; however the metabolic mechanism of UDP-glucuronosyltransferases (UGTs) in the process remains to be investigated. In this study, the kinetics of bergenin glucuronidation by pooled human liver microsomes (HLMs) and 12 recombinat UGT isozymes were investigated. The glucuronidation of bergenin can be shown in HLMs with a Km value of 231.62 ± 14.08 µm and a Vmax value of 2.17 ± 0.21 nmol/min/(mg protein). Among the 12 human UGTs investigated, UGT1A1 was identified as the major isoform catalyzing the glucuronidation of bergenin [Km value of 200.37 ± 26.73 µm and Vmax value of 1.88 ± 0.26 nmol/min/(mg protein)]. The bergenin glucuronosyltransferase activities in HLMs and UGT1A1 were inhibited by phenylbutazone, estradiol and bilirubin. The results demonstrate that bergenin glucuronidation in HLMs is specifically catalyzed by UGT1A1.
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Benzopiranos/metabolismo , Glucuronídeos/metabolismo , Glucuronosiltransferase/metabolismo , Benzopiranos/análise , Glucuronídeos/análise , Glucuronosiltransferase/química , Humanos , Hidrólise , Cinética , Microssomos Hepáticos/metabolismoRESUMO
Bergenin is the major component of Ardisia creanta sims and Rodgersia sambucifolia hemsl with many biological activities. Although bergenin has been used to treat human diseases in China for man years, there is no report regarding its metabolism. This is the first report to separate and identify the metabolites of bergenin in vivo. In the study, HPLC/Q-TOF-MS/MS was used to investigate the metabolites of bergenin in vivo by analyzing the rat body fluid and feces samples. Three metabolites of bergenin were finally identified by the TIC chromatograms, and the structures were also confirmed by their MS(2) spectra.
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Benzopiranos/análise , Benzopiranos/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Animais , Ardisia/química , Benzopiranos/sangue , Benzopiranos/urina , Bile/química , Bile/metabolismo , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/metabolismo , Fezes/química , Ratos , Ratos WistarRESUMO
Four undescribed highly oxidized and rearranged limonoids, secotrijugins A-D, were purified from the leaves and twigs of Trichilia sinensis. Within them, secotrijugin A was characterized as a rare 30-nortrijugin-type limonoid with an unusual cleavage of 1,14-ether bond, secotrijugins B and C represented new examples with the cleavage of δ-lactone ring D, and secotrijugin D was a rare trijugin-type limonoid with an unusual 2,6-oxygen bridge. The structures of limonoids were characterized by means of spectroscopic analysis and ECD calculations. The cellular screening revealed that secotrijugin B was the most active against LPS-stimulated NO production in BV-2 cells, which played an anti-inflammatory role by downregulating COX-2 and iNOS protein expression. The further in vivo experiments confirmed that secotrijugin B had strong in vivo anti-inflammatory effect via suppressing NO and ROS generation.
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Limoninas , Meliaceae , Limoninas/farmacologia , Anti-Inflamatórios/farmacologiaRESUMO
BACKGROUND AND OBJECTIVES: Multiple reforms aimed at improving the Chinese population's health have been introduced in recent years, including several designed to improve access to innovative drugs. We sought to review current factors affecting access to innovative drugs in China and to anticipate future trends. METHODS: Targeted reviews of published literature and statistics on the Chinese healthcare system, medical insurance and reimbursement processes were conducted, as well as interviews with five Chinese experts involved in the reimbursement of innovative drugs. RESULTS: Drug reimbursement in China is becoming increasingly centralized due to the removal of provincial pathways, the establishment of the National Healthcare Security Administration and the implementation of the National Reimbursement Drug List (NRDL), which is now the main route for drug reimbursement in China. There is also an increasing number of other channels via which patients may access innovative treatments, including various types of commercial insurance and special access. Health technology assessment (HTA) and health economic evidence are becoming pivotal elements of the NRDL decision-making process. Alongside the optimization of HTA decision making, innovative risk-sharing agreements are anticipated to be increasingly leveraged in the future to optimize access to highly specialized technologies and encourage innovation while safeguarding limited healthcare funds. CONCLUSIONS: Drug public reimbursement in China continues to align more closely with approaches widely used in Europe in terms of HTA, health economics and pricing. Centralization of decision-making processes for public reimbursement of innovative drugs allows consistency in assessment and access, which optimizes the improvement of the Chinese population's health.
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A sensitive and selective liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) was developed and validated for the determination of salbutamol in human plasma and urine, and successfully applied to the pharmacokinetic study of salbutamol in Chinese healthy volunteers after inhalation of salbutamol sulfate aerosol. Salbutamol and the internal standard (IS) acetaminophen in plasma and urine were extracted with ethyl acetate, separated on a C(18) reversed-phase column, eluted with mobile phase of acetonitrile-ammonium acetate (5 m m; 30:70, v/v), ionized by positive ion pneumatically assisted electrospray and detected in the multi-reaction monitoring mode using precursor â product ions of m/z 240.2 â 148.1 for salbutamol and 152 â 110 for the IS. The lower limits of quantitation of salbutamol in human plasma and urine by this method were 0.02 and 1 ng/mL, respectively. The specificity, matrix effect, recovery, sensitivity, linearity, accuracy, precision and several stabilities were validated for salbutamol in human plasma and urine. In conclusion, the validation results showed that this method is robust, specific and sensitive, and can successfully fulfill the requirement of clinical pharmacokinetic study of salbutamol in healthy Chinese volunteers.
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Albuterol/sangue , Albuterol/urina , Cromatografia de Fase Reversa/métodos , Espectrometria de Massas em Tandem/métodos , Acetaminofen , Adulto , Albuterol/farmacocinética , Área Sob a Curva , Estabilidade de Medicamentos , Humanos , Modelos Lineares , Masculino , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
The aim of this study is to establish an HPLC method for simultaneous determinations of mifepristone and its metabolites, mono-demethylated mifepristone, di-demethylated mifepristone and C-hydroxylated mifepristone in plasma and to evaluate the pharmacokinetic characteristics of mifepristone tablet. Twenty healthy female Chinese subjects were recruited and a series of blood samples were collected before and after 0.25, 0.5, 1.0, 1.5, 2.0, 4.0, 8.0, 12.0, 24.0, 48.0, 72.0 and 96.0 hours administration by a single oral dose of 75 mg mifepristone tablet. Mifepristone and its three metabolites were extracted from plasma using ethyl acetate and determined by high performance liquid chromatography. The main pharmacokinetic parameters of mifepristone and its metabolites, including Cmax, tmax, MRT, t(1/2), V, CL, AUC(0-96 h) and AUC(0-infinity), were calculated by Drug and Statistical Software Version 2.0. The simple, accurate and stable method allows the sensitive determinations of mifepristone and its metabolites in human plasma up to 4 days after oral administration of 75 mg mifepristone tablet and the clinical applications of their pharmacokinetic studies.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Mifepristona/metabolismo , Mifepristona/farmacocinética , Administração Oral , Área Sob a Curva , Povo Asiático , Disponibilidade Biológica , Feminino , Humanos , Mifepristona/administração & dosagem , ComprimidosRESUMO
The study aimed to compare and evaluate the bioequivalence of Calcigard-10 softgel and Adalat 10 capsule in healthy Chinese volunteers in a randomized, two-way cross over study design with a washout period of 7 days. A sensitive and reproducible electro-spray ionization liquid chromatography-mass spectrometry (ESI-LCMS) assay was developed and validated to determine nifedipine in human plasma using nitrendipine as internal standard. Nifedipine and nitrendipine were extracted from plasma using liquid-liquid extraction with methylene chloride as extraction solvent. The separation was performed by a Diamonsil ODS column (150 x 4.6 mm, 5 microm). The mobile phase was consisted of acetonitrile-5 mM ammonium acetate (52:48, v/v), delivered at flow rate of 1 mL/min. The 90% confidence intervals for the ratio values of logarithmic transformed Cmax and AUC were calculated to evaluate the bioequivalence of two preparations. The values of Cmax (92.3-112.7%), AUC0-t (84.5-95.1%) and AUC0-inf (84.4-95.5%) are within the interval criterion of 70-143% for Cmax and 80-125% for AUC. The Calcigard-10 softgel and Adalat 10 capsule are bioequivalent.