Pradefovir Treatment in Patients With Chronic Hepatitis B: Week 24 Results From a Multicenter, Double-Blind, Randomized, Noninferiority, Phase 2 Trial.

BACKGROUND: Pradefovir is a liver-targeted prodrug of adefovir, a nucleoside/nucleotide analogue with antiviral activity against hepatitis B virus (HBV) DNA polymerase. This phase 2 study compared the efficacy and safety of oral pradefovir (30, 45, 60, or 75 mg) versus tenofovir disoproxil fumarate (TDF; 300 mg) and aimed to identify the most appropriate dose of pradefovir for the forthcoming phase 3 study. METHODS: Treatment-naive and experienced (not on treatment >6 months) patients with chronic hepatitis B were eligible. RESULTS: A total of 240 participants were randomized and treated in the study (48 per group). Approximately 80% were hepatitis B e antigen (HBeAg) positive, and 10% had liver cirrhosis. The reductions from baseline in HBV DNA levels achieved at week 24 were 5.40, 5.34, 5.33, and 5.40 log10 IU/mL, with pradefovir doses of 30-, 45-, 60-, and 75-mg, respectively, compared with 5.12 log10 IU/mL with TDF. However, HBeAg loss was attained by more participants who received 45-, 60-, or 75-mg pradefovir than by those receiving TDF (12%, 6%, and 9% vs 3%). The TDF group exhibited a more significant increase in serum creatinine than the pradefovir 30- and 45-mg groups, and serum phosphate levels were comparable among all groups. Most adverse events (AEs) were mild (grade 1). No treatment-related severe AEs were reported. Overall, AEs and laboratory abnormalities were comparable to those in the TDF group. CONCLUSIONS: Pradefovir and TDF exhibited comparable reductions in HBV DNA levels. All treatments were safe and well tolerated. CLINICAL TRIALS REGISTRATION: NCT00230503 and China Drug Trials CTR2018042.

Exploring lipid biomarkers of coronary heart disease for elucidating the biological effects of gelanxinning capsule by lipidomics method based on LC-MS.

High-throughput lipidomics technology was used to explore the potential therapeutic targets and mechanism of action of gelanxinning capsule on rat model with coronary heart disease (CHD). This study attempts to provide a novel method to interpret the molecular mechanism of traditional medicine. The lipid markers of CHD were determined by full-scan analysis based on ultra-performance liquid chromatography-high-definition mass spectrometry. Then, the metabolic changes associated with gelanxinning capsule treatment via the modulation of lipid biomarkers and pathway in rats were characterized. After gelanxinning treatment, the metabolic profile tended to recover compared with the model group. A total of 26 potential biomarkers were identified to represent the disorders of lipid metabolism in CHD animal model, of which 19 were regulated by gelanxinning capsule administration, and four metabolic pathways such as glycerophospholipid metabolism, sphingolipid metabolism, glycosylphosphatidylinositol-anchor biosynthesis, and glycerolipid metabolism were involved. From the pathway analysis, it was found that glycerophospholipid metabolism and sphingolipid metabolism with significant differences have the potential to be regarded as new targets for the treatment of CHD. Gelanxinning capsule with its good therapeutic effect protects against CHD by regulating lipid biomarkers and pathway from lipidomics-guided biochemical analysis.

Characterization of chemical constituents and absorbed components, screening the active components of gelanxinning capsule and an evaluation of therapeutic effects by ultra-high performance liquid chromatography with quadrupole time of flight mass spectrometry.

We revealed the potential biomarker and pathway of gelanxinning capsule on rat model with coronary heart disease, which aims to clarify holistic therapeutic effect and predict quality-markers of gelanxinning capsule. Ultra-high performance liquid chromatography coupled with mass spectrometry based on metabolomics technique was used to find the biomarkers and related metabolic pathways of coronary heart disease model, which evaluates the intervention effect of gelanxinning capsule. Using serum pharmacochemistry of traditional Chinese medicine and Pearson correlation analysis, effective ingredients in serum is analyzed to characterize the activity of gelanxinning capsule on coronary heart disease under valid state. A total of 20 biomarkers from coronary heart disease were identified and 12 of them were regulated by gelanxinning capsule treatment, which is mainly involved in sphingolipid metabolism and glycerophospholipid metabolism. With the high sensitivity liquid chromatography coupled with mass spectrometry technology, a total of 46 compounds from gelanxinning capsule were identified in vitro and 25 of them were absorbed in blood. The correlation analysis of serum biomarkers and absorbed components was used to find 11 compounds as quality-markers to be responsible for the efficacy of gelanxinning capsule. This strategy was successfully applied to screening of potential mechanism and quality-markers from herbal medicine.