ABSTRACT
RATIONALE: GW1929 is a potent PPAR-γ activator. To fully understand its mechanism of action, it is necessary to study the in vitro and in vivo metabolism. METHODS: For in vitro metabolism, GW1929 was incubated with rat hepatocytes at 37°C for 2 h. For in vivo metabolism, rats were orally administered with GW1929 at a single dose of 10 mg/kg and plasma, urinary and fecal samples were collected at defined time points. All the samples were analyzed by the developed ultra-high-performance liquid chromatography combined with tandem mass spectrometry. The structures of metabolites were proposed according to their accurate masses and product ions. RESULTS: A total of 17 metabolites, including seven glucuronide conjugates, were detected and structurally identified. M4 (hydroxylation), M13 (demethylation) and M14 (hydroxylation) were the most abundant metabolites. The metabolic pathways of GW1929 referred to hydroxylation, demethylation, deamination and glucuronidation. CONCLUSIONS: The present study provided new information on the in vitro and in vivo metabolic profiles of GW1929 which will be helpful for a better understanding of the mechanism of the elimination of GW1929.
Subject(s)
Benzophenones/chemistry , Benzophenones/metabolism , Chromatography, High Pressure Liquid/methods , Tandem Mass Spectrometry/methods , Tyrosine/analogs & derivatives , Animals , Benzophenones/administration & dosage , Female , Hepatocytes/chemistry , Hepatocytes/metabolism , Hydroxylation , Male , Molecular Structure , Rats , Tyrosine/administration & dosage , Tyrosine/chemistry , Tyrosine/metabolismABSTRACT
BACKGROUND: Bone fractures are a common occurrence, and, according to clinical investigations, approximately 5% to 10% of patients with fractures will suffer from delayed healing or even non-healing. The high efficacy of traditional Chinese medicine in promoting fracture healing has been fully verified over a long history of diagnosis and treatment. Traditional Chinese medicine has a long history of applying Chinese herbs to treat fractures. Cervus and cucumis polypeptide injection has been widely used to promote fracture healing after fracture surgery in clinic, but its efficacy and safety are controversial. For the above reasons, the purpose of this study is to systematically evaluate the efficacy and safety of cervus and cucumis polypeptide injection in promoting fracture healing after bone fracture surgeries and to provide a theoretical basis for the selection of appropriate treatment measures for delayed healing of patients with fractures. METHODS: A total of 8 databases were searched, including the non-Chinese-language databases PubMed, The Cochrane Library, Web of Science, and Embase and the Chinese databases Chongqing VIP Chinese Journal Service Platform (VIP), Wanfang Data Knowledge Service Platform (Wanfang Data), SinoMed and Chinese National Knowledge Infrastructure (CNKI). The databases were queried for publicly released randomized controlled trials of the effectiveness and safety of Cervus and Cucumis polypeptide injection for fracture healing after surgical treatment, and no language restrictions were imposed. The software Review Manager 5.3 was used to evaluate the quality of the selected documents, and Stata 12.0 software was used for statistical analysis. RESULTS: This review will be to assess the efficacy and safety of cervus and cucumis polypeptide injection in promoting fracture healing after bone fracture surgeries. CONCLUSION: Our study will use systematic evaluation to objectively evaluate the efficacy and safety of cervus and cucumis polypeptide injection in promoting fracture healing after fracture surgery. It will provide theoretical basis for guiding clinical practice and benefit more patients. ETHICS AND DISSEMINATION: This study is a systematic review that does not require ethical approval and meets the requirements of protocol for a systematic review and meta-analysis. At the same time, this study does not involve the recruitment of patients. All data are from published academic papers. PROTOCOL AND REGISTRATION: A protocol had been registered for this systematic review and meta-analysis in PROSPERO. (registration number: CRD42019120965).
Subject(s)
Cucumis , Deer , Fracture Healing/drug effects , Fractures, Bone/drug therapy , Medicine, Chinese Traditional/methods , Peptides/therapeutic use , Animals , Humans , Injections , Medicine, Chinese Traditional/adverse effects , Peptides/administration & dosage , Peptides/adverse effects , Randomized Controlled Trials as Topic , Research DesignABSTRACT
OBJECTIVE: To evaluate the antibacterial activity of Ciprofloxacin, Amikacin in combination with beta-lactams against Pseudomonas aeruginosa strains in vitro, to optimize treatment regime for antibiotics on the basis of pharmacokinetics (PK)/pharmacodynamics (PD) and drug sensitivity tests. Methods With checkerboard titration method, the minimal inhibitory concentrations (MIC) of a combination of antibiotics in different concentrations for 33 clinically isolated Pseudomonas aeruginosa strains were determined by broth dilution. Fractional inhibitory concentrations (FIC) were calculated for judging synergic effect of antibiotics. RESULTS: The combination of Amikacin and Ceftazidime showed synergic effects (accounting for 57.6%). The combinations of Ciprofloxacin with Ceftazidime, Cefepime, Imipenem/Cilastatin, Meropenem showed synergic or additive effect. In the study with PK/PD, C(max)/MIC was the principal parameters for evaluation of aminoglycoside and fluoroquinolone antibiotics, while T > MIC was the principal parameter to be used to evaluate beta-lactams antibiotics. CONCLUSION: When antibiotics are used in combination, MICs can be reduced significantly and antibacterial activities are enhanced remarkably. The combination of antibiotics results mainly in synergic or additive effect, and no inhibitory effect is observed. PK/PD analysis plays an important role in planning optimal combination regime to raise clinical efficacy.
