Access to innovative drugs and the National Reimbursement Drug List in China: Changing dynamics and future trends in pricing and reimbursement.

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.

Secotrijugins A-D, four highly oxidized and rearranged limonoids from Trichilia sinensis and their anti-inflammatory activity.

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.

Medication therapy of high-dose methotrexate: An evidence-based practice guideline of the Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society.

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.

Pharmacokinetics and vasodilating effect study of beraprost sodium in healthy volunteers.

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.

Evidence-based Guideline for Therapeutic Drug Monitoring of Vancomycin: 2020 Update by the Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society.

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.

Simultaneous determination of paraquat and diquat in human plasma by HPLC-DAD: Its application in acute poisoning patients induced by these two herbicides.

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.

Bi and oxygen defects improved visible light photocatalysis with BiOBr nanosheets.

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.

Simultaneous Determination of Multiple Active Components from Bushen Pills and Application in a Pharmacokinetic Study in Rats.

Bushen Pills (BSPs), as a traditional Chinese medicine (TCM), is widely used in clinic to enrich Yang, nourish Yin, stem essence, and strengthen kidneys. Two chromatographic methods, liquid chromatography-mass spectrometry (LC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), were applied to analyze the multiple active components of BSPs in dosage form for quality evaluation and in rat plasma for pharmacokinetics study, respectively. Three active constituents of BSPs, including paeoniflorin (PF), berberine hydrochloride (BBR), and schizandrin (SCH), were simultaneously determined by the established LC-MS method with electrospray ionization (ESI) in positive selected ion monitoring (SIM) mode at / 503.

Serum metabolomic profiling in patients with Alzheimer disease and amnestic mild cognitive impairment by GC/MS.

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.

Synonymous mutation rs2515641 affects CYP2E1 mRNA and protein expression and susceptibility to drug-induced liver injury.

To evaluate whether the synonymous mutant rs2515641 could affect cytochrome P450 2E1 () expression and the response to acetaminophen (APAP) or triptolide (TP) treatment. HepG2 cells were transfected with lentiviral vector containing either or . Some of these recombinant cells were then treated with APAP or TP.

CYP2E1 and miRNA-378a-3p contribute to acetaminophen- or tripterygium glycosides-induced hepatotoxicity.

Increased expression of CYP2E1 may represent the main factor contributing to oxidative stress-mediated liver damage in drug-induced liver injury (DILI). However, the regulation mechanism of CYP2E1 expression is poorly described. The present study was aimed to investigate the role of CYP2E1 in acetaminophen (APAP)- or tripterygium glycosides (TG)-induced hepatotoxicity as well as the regulation of CYP2E1 and miR-378a-3p expression by APAP or TG.

Therapeutic drug monitoring of valproic acid.

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.

Analysis of phenytoin drug concentration for evaluation of clinical response, uncontrolled seizures and toxicity.

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.

The Impact of Antiepileptic Drugs on Vitamin Levels in Epileptic Patients.

Background: The impact of antiepileptics on serum vitamin levels is controversial and uncertain. With no clear conclusions on the impact of antiepileptics on serum levels of vitamins, there is a need for further clinical studies in order to ascertain the impact of old and newer antiepileptic drugs on serum levels of vitamins in epileptic patients, thus accomplishing a suitable usage of vitamins supplementation.

Objective: The intention of the present research is to confirm the hypothesis of whether or not vitamin levels are altered with antiepileptic drugs.

Pharmacokinetic, metabolic profiling and elimination of brusatol in rats.

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.

Pharmacokinetics and bioequivalence study of tetramethylpyrazine phosphate tablets after single-dose administration in healthy Chinese male subjects .

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.

A simple and economical method of gas chromatography-mass spectrometry to determine the presence of 6 pesticides in human plasma and its clinical application in patients with acute poisoning.

An economical, rapid, and sensitive method of gas chromatography-mass spectrometry (GC-MS) was developed and validated to determine the presence of six pesticides (dichlorvos, acetochlor, atrazine, chlorpyrifos, α-endosulfan, and β-endosulfan) in human plasma. The pesticides were extracted with acetonitrile and concentrated using anhydrous sodium sulfate. Then, the target compounds were analyzed and quantified with GC-MS using borneol as an internal standard.

Comparison of New Liquid Chromatography-Mass Spectrometry Method and Enzyme-Multiplied Immunoassay Technique for Routine Therapeutic Drug Monitoring of Vancomycin in Chinese Patients.

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).

Therapeutic Drug Monitoring of Phenytoin by Simple, Rapid, Accurate, Highly Sensitive and Novel Method and Its Clinical Applications.

Background: Phenytoin has very challenging pharmacokinetic properties. To prevent its toxicity and ensure efficacy, continuous therapeutic monitoring is required. It is hard to get a simple, accurate, rapid, easily available, economical and highly sensitive assay in one method for therapeutic monitoring of phenytoin.

A comparison of liquid chromatography-tandem mass spectrometry (LC-MS/MS) and enzyme-multiplied immunoassay technique (EMIT) for the determination of the cyclosporin A concentration in whole blood from Chinese patients.

Cyclosporin A (CyA) is an immunosuppressive agent widely used in clinical therapy. In the therapeutic process, the blood concentration of CyA should be monitored to avoid or prevent rejection and toxicity. The objectives of this study were to compare the correlation of liquid chromatography-tandem mass spectrometry (LC-MS/MS) and enzyme-multiplied immunoassay technique (EMIT) for the determination of the CyA concentration in human blood and to provide evidence for the rational usage of EMIT in clinical practice.

Comparison of the docetaxel concentration in human plasma measured with liquid chromatography-tandem mass spectrometry (LC-MS/MS) and a nanoparticle immunoassay and clinical applications of that assay.

To determine the feasibility of using a nanoparticle immunoassay for clinical therapeutic drug monitoring (TDM) of docetaxel concentrations, a sensitive and simple method of liquid chromatography-tandem mass spectrometry (LC-MS/MS) was established to measure the docetaxel concentration in human plasma and the results of LC-MS/MS and the immunoassay were compared. Docetaxel and paclitaxel (the internal standard, or IS) in human plasma were extracted through protein precipitation, separated on a Diamonsil C18 column (150 mm × 4.6 mm, 5 μm), ionized with positive ions, and detected with LC-MS/MS in multi-reaction monitoring (MRM) mode.

Simple, rapid and highly sensitive HPLC method for measurement of Lamotrigine in human plasma and its clinical applications.

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 C (150mm×4.

Determination of brusatol in plasma and tissues by LC-MS method and its application to a pharmacokinetic and distribution study in mice.

Objectives: The quassinoid brusatol, which can be isolated from Brucea javanica (L.) Merr., becomes popularly studied because of its anti-tumor activity.

Bioequivalence Study of Warfarin in Healthy Chinese Volunteers With a Validated High-Performance Liquid Chromatography-Mass Spectrometry Method.

This study was designed to investigate the pharmacokinetics of an innovative film-coated warfarin sodium tablet and to compare it with the marketed sugar-coated warfarin sodium tablet in humans. A single-dose, open-label, randomized, two-way crossover study was performed in 24 healthy Chinese male volunteers. They were administered 2.