Human carboxylesterase (CES) and arylacetamide deacetylase (AADAC) are important numbers of the serine esterase superfamily. They are involved in hydrolytic procedure of human endogenous cholesteryl esters, as well as drug metabolism, activation and detoxication. They are closely related to the personalized medication of drugs, especially for prodrugs. This review summarizes their structure and distribution, metabolic characteristics and research progress in recent years, which will provide a reference for new drug development and rational drug design.

Alcoholic liver disease (ALD) includes a spectrum of disorders ranging from asymptomatic steatosis, alcoholic steatohepatitis (ASH), fibrosis and cirrhosis. According to epidemical statistics, ALD has been ranked as the second major cause of liver diseases in China. Many animal models have been made in the study of potential therapies. However, in most of the models, the pathological changes are not always consistent with those in patients. There are three widely used short-term animal models of ALD:the acute alcoholic liver injury model, Gao-binge steatohepatitis model and CCl₄-alcohol diet induced liver fibrosis model. In this study, we evaluated the pathological responses of these models and compared the responses with the clinical parameters. The liver/body weight ratio was increased and liver histological lesions were induced in alcoholic groups in the three models, while the levels of biochemical parameters and inflammatory factors were affected by different type of treatments. In the acute alcoholic model, the mRNA levels of interleukin-6 (IL-6) and C-C motif chemokine receptor-2 (CCL2) were surprisingly decreased, which was consistent with the transcriptome profile in patients (P < 0.05), but the serum ALT and AST level, were not changed. In Gao-binge model, both AST/ALT and triglyceride levels were significantly induced by alcoholic consumption (P < 0.05), along with the gene expression levels of hepatic IL-6 and CCL2 (P < 0.05). These data were similar in tendency to the pathological indicators of hepatitis patients. In liver fibrosis model, although histological section indicated obvious fibrotic lesion and little lipid accumulations, other indexes were barely changed. In conclusion, the Gao-binge model induced similar pathological patterns to those of steatohepatitis patients. Gao-binge model might be ideal for study of ALD, especially alcoholic steatohepatitis. In addition, we also found that hepatic gene expression of CCL2 was impacted differently at various stages of ALDs, which can be considered as a potential biomarker.

It is generally assumed that study of in vitro dissolution can reveal the in vivo behavior and bioavailability of a drug. The dissolution test indisputably plays a vital role in the research and development of pharmaceutical preparations as well as routine quality control of approved drugs. In order to develop an ideal dissolution method, the physicochemical properties of drug and the characteristics of its dosage form should be considered, and a proper dissolution condition be established to simulate the in vivo dissolution behavior of drugs. The new dissolution method should have the required characteristics of accuracy and durability, but also could distinguish pharmaceutic preparations with different quality. In recent years, there have been more and more reports on the establishment and verification of dissolution methods for oral solid dosage forms. However, there is very few review articles on the topic. According to the latest guidelines by domestic and foreign drug organizations, this review paper is prepared to summarize the most important skills and progress in the development of dissolution methods for oral solid preparations. The aim is to provide a reference for the development and validation of new dissolution methods.

This study was carried out to investigate the pharmacokinetics/bioequivalence of levornidazole disodium phosphate by using stable isotope labeled drug, evaluated the pharmacokinetic profile and confirmed the prodrug characteristics of levornidazole disodium phosphate in monkey. Levornidazole (Drug A) and stable isotope ¹⁵N labeled levornidazole disodium phosphate (Drug B) were mixed with equal mole amount (experiment Ⅰ); stable isotope ¹⁵N labeled levornidazole disodium phosphate (Drug B) and levornidazole disodium phosphate (Drug C) were mixed with equal mole amount, respectively. After giving the mixed drugs to the monkey, the concentration of ¹⁵N-levornidazole disodium phosphate, levornidazole disodium phosphate, ¹⁵N-levornidazole and levornidazole in plasma samples of pre-dosing and 24 h after administration were analyzed by a liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method. Pharmacokinetic calculations were performed through non-compartmental analysis using WinNonlin software. Two-sided 90% confidence intervals (CI) were used to evaluate the bioequivalence of two drugs. The results showed that levornidazole disodium phosphate was metabolized to levornidazole rapidly after administration, the body exposure were increased with the dosage. The method of bioequivalence used in this study was different from the traditional two periods, crossover design. By using the method of this study, the effects of administration period, intra-individual variability, and sequence of administration on bioequivalence were avoided. The results of this study had successfully supported the pharmacokinetic and bioequivalence study of this drug in human using the same approach.

Severe acute pancreatitis (SAP) is characterized by both local and systemic inflammatory responses. This study was designed to develop a site-specific delivery strategy for SAP therapy using celastrol (CLT). First, murine RAW264.7 cells were used as a model of macrophage cell line, cell membranes were obtained by emptying intracellular contents via hypotonic lysing, mechanical membrane disruption, and differential centrifugation. Poly(ethylene glycol) methyl ether-block-poly(lactic-co-glycolic acid) (PEG-PLGA) nanoparticles (NPs) were then prepared by sonication. With the collected membrane materials, macrophage membrane coated PEG-PLGA NPs (RNPs) were then prepared by extrusion through a 400 nm polycarbonate membrane. Biodistribution study in rats with SAP showed RNPs selectively accumulated in the inflamed pancreatic tissues. Compared with CLT loaded NPs, CLT loaded RNPs were proven to effectively attenuate local pancreatic inflammation and systemic inflammation in rats with SAP.

Follow-on drug approach is to follow-up and make-up of the innovation of pioneering drugs. Since the millennium new molecular entities (NME) have experienced ample optimization, and the patents have claimed in wide ranges, as well as the drug administration requires NME being superior or non-inferior to the existing drugs of the same class. These situations have made the space of follow-on drug innovation narrow and smaller than before. The follow-on drug approach can be concisely differentiated into two aspects:one is to start from the chemistry of small molecules, which are performed with a niche-targeting manipulation to optimize the safety, efficacy and (or) convenience for dose superior to the existing drugs; another proceeds with the macromolecule targets. Based on the knowledge of the mechanism of action or of target mutation, active compounds are constructed through complementary binding or by the reaction mechanism. In this article successful examples are briefly described to illustrate the features of follow-on drug approach.

Vancomycin has been widely prescribed as the first-line antibiotic in the treatment of methicillin-resistant Staphylococcus aureus and other serious Gram-positive infections. Due to its large pharmacokinetic (PK) variability and narrow therapeutic range, it requires optimization of dosage to achieve target exposure. In this study, SmartDose, a decision support system for individualization of vancomycin dosage is developed using the maximum a posterior Bayesian estimation (MAPB) by the open-source language R combined with the population PK characteristics of vancomycin in Chinese patients. It provides initial design and adjustment of dose regimens based on the therapeutic drug monitoring (TDM) results, as well as a user-defined module to facilitate optimal vancomycin therapy. SmartDose has a high computational reliability, which is validated by NONMEM, the golden standard PK software. Meanwhile, SmartDose is established as a web-based application and its operational flexibility makes it an efficient tool for vancomycin dose optimization in routine clinical settings.

Ginsenoside Rg1 is one of the main active components of ginseng with various pharmacological activities including anti-inflammatory, anti-oxidation, anti-aging, anti-tumor and anti-apoptosis. Ginsenoside Rg1 plays a protective role in multiple tissues and organs, which shows the multiple targeting properties of the pharmacological effects. Recently, a number of studies have demonstrated that ginsenoside Rg1 has a protective role in the liver due to its multiple pharmacological effects. In chemical liver injury models, or in other liver injury models, ginsenoside Rg1 can alleviate liver necrosis induced by oxidative stress and inflam-mation. This article provides a review of the recent studies on the efficacy of ginsenoside Rg1 in the treatment of various liver damage and the molecular mechanism.

Two new diarylheptane derivatives were isolated from Rhizoma Zingiberis by Diaion HP-20, MCI Gel CHP-20, ODS, silica gel column and reverse phase semi-prepared high performance liquid chromatography. Their structures were elucidated by spectrum technology (MS, UV, IR, NMR), which were identified as 3-keto-5R-ethoxy-1-(3-methoxy-4-hydroxyphenyl)-7-(3, 4-dihydroxyphenyl)heptane (1) and 3-keto-5R-ethoxy-1-(3-methoxy-4-hydroxyphenyl)-7-(3-methoxy-4, 5-dihydroxyphenyl)heptane (2). Compounds 1 and 2 are new compounds.

As a new generation of anti-tumor drugs, taxanes has a good clinical efficacy in the treatment of ovarian cancer, breast cancer, non-small cell lung cancer, head and neck cancer. However, low bioavailability of oral administration from low water solubility and low permeability significantly limited the development of their oral applications. Currently, the marketed preparations were non-oral drug preparations, and the injection contained a large number of surfactants (cremophor EL or Tween 80) and organic solvents (ethanol), which could result in fluid retention, hypersensitivity and other side effects, as well as poor compliance. Oral preparation will be an ideal form for development of taxanes medicines. According to the research by our and other groups in recent years, we investigate the technical strategies enhancing the water solubility and absorptive permeability to improve their oral bioavailability. Among them, we emphasize the application prospects of crystallography technology, and provide a theoretical basis to guide future research in the development of oral preparations for taxanes.