Angina Pectoris ; drug therapy ; Animals ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Phytotherapy ; Technology, Pharmaceutical

Aged ; Animals ; Cyclosporine ; adverse effects ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Graft Rejection ; drug therapy ; prevention & control ; Humans ; Immunosuppressive Agents ; therapeutic use ; Kidney Diseases ; chemically induced ; prevention & control ; Kidney Transplantation ; Phytotherapy

The study aims to evaluate the bioequivalence of valsartan hydrochlorothiazide tablets, and to investigate the potential cause of bioinequivalence. This was a single-center study with an open, randomized double-way crossover design. Test and reference preparations containing 160 mg of valsartan and 25 mg of hydrochlorothiazide were given to 36 healthy male volunteers. Plasma concentrations of valsartan and hydrochlorothiazide were determined simultaneously by LC-MS/MS. The pharmacokinetic parameters and relative bioavailability were calculated, while the bioequivalence between test and reference preparations were evaluated. The dissolution profiles of test and reference preparations in four different mediums were determined via dissolution test and HPLC. The similarity was investigated according to the similarity factors (f2). The F(o-t) and F(0-infinity) were (139.4 +/- 65.2)% and (137.5 +/- 61.2)% for valsartan of test preparations. It led to get the conclusion that test and reference preparations were not bioequivalent for valsartan. A significant difference was observed between test and reference tablets in the valsartan dissolution test of pH 1.2 hydrochloric acid solution. The key factor of the bioinequivalence might be that dissolution of valsartan in acid medium has marked difference between two preparations.

The study aims to evaluate the bioequivalence of valsartan hydrochlorothiazide tablets, and to investigate the potential cause of bioinequivalence. This was a single-center study with an open, randomized double-way crossover design. Test and reference preparations containing 160 mg of valsartan and 25 mg of hydrochlorothiazide were given to 36 healthy male volunteers. Plasma concentrations of valsartan and hydrochlorothiazide were determined simultaneously by LC-MS/MS. The pharmacokinetic parameters and relative bioavailability were calculated, while the bioequivalence between test and reference preparations were evaluated. The dissolution profiles of test and reference preparations in four different mediums were determined via dissolution test and HPLC. The similarity was investigated according to the similarity factors (f2). The F(o-t) and F(0-infinity) were (139.4 +/- 65.2)% and (137.5 +/- 61.2)% for valsartan of test preparations. It led to get the conclusion that test and reference preparations were not bioequivalent for valsartan. A significant difference was observed between test and reference tablets in the valsartan dissolution test of pH 1.2 hydrochloric acid solution. The key factor of the bioinequivalence might be that dissolution of valsartan in acid medium has marked difference between two preparations.
Administration, Oral ; Adolescent ; Adult ; Angiotensin II Type 1 Receptor Blockers ; administration & dosage ; adverse effects ; blood ; pharmacokinetics ; Antihypertensive Agents ; administration & dosage ; adverse effects ; blood ; pharmacokinetics ; Area Under Curve ; Chromatography, Liquid ; Cross-Over Studies ; Drug Liberation ; Humans ; Hydrochlorothiazide ; administration & dosage ; adverse effects ; blood ; pharmacokinetics ; Male ; Tablets ; Tandem Mass Spectrometry ; Therapeutic Equivalency ; Valsartan ; administration & dosage ; adverse effects ; blood ; pharmacokinetics ; Young Adult

Trypanosoma is a human parasite severely affecting poor tropical areas.However,current frontline drugs for Trypanosoma treatment have severe side-effects with decreased effectiveness.Based on the fact that aminoacyl-tRNA synthetase is a bonafide drug target for several microorganisms,including bacteria and fungi,it is plausible that it may also be effective target of Trypanosoma.The Trypanosoma brucei leucyl-tRNA synthetase(tbLeuRS)was cloned,expressed and purified to develop an in vitro enzymatic assay system.The assay conditions were further optimized for the effective screening of tbLeuRS inhibitors thus establishing an anti-Trypanosoma drug screening system targeting tbLeuRS.The results indicated that this system can be employed for the effective screening of anti-Trypanosoma drugs with satisfactory specificity.In addition,this system can also be used for compound optimization,as well as IC50 testing.Using this system a series of compounds are identified that are effective Trypanosoma inhibitors without toxicity to human cells.Therefore,targeting tbLeuRS may represent a new venue for the development of anti-Trypanosoma drugs.

AIM:To investigate the potential of differentiatng into myocytes of the granulocyte colony-stimulating factor(G-CSF)-mobilized CD34 + cells. METHODS: Three hours after intraperitoneal injecction of isoprenaline(ISO) to develop acute ischemic model, rats' bone marrow hematopoietic stem cells were mobilized to the site of myocardial infarction by G-CSF. The techniques of immunohistochemisty and HE stain were used to detect the infiltration of CD34 + cells and the regeneration of myocytes in the infarct zones. RESULTS: 24 hours after administration of ISO , a large amount of infiltrative monocytes and regenerative myocytes which were CD34 positive expression could be found in the infarct zones of the G-CSF treatment group, while majority of the infiltrative inflammatory cells in control group were neutrophils and there was no infiltrative cells and myocytes which were CD34 positive expressio, 2 weeks after administration of ISO, there were a plenty of scar in control group, but not in the G-CSF treatment group. CONCLUSION: G-CSF-mobilized CD34 + cells possess the potential to differentiate into myocytes and it may be used in treating acute myocardial infarction.

A rapid, sensitive and convenient LC-MS/MS method was developed for the determination of γ-aminobutyric acid (GABA) in human plasma. d2-γ-Aminobutyric acid (d2-GABA) was synthesized as internal standard (IS). After extraction from human plasma by protein precipitation with acetonitrile, all analytes were separated on a Luna HILIC column (100 mm x 3.0 mm, 3 μm) using an isocratic mobile phase of water: acetonitrile: formic acid (20 : 80 : 0.12) with a flow rate of 0.5 mL x min(-1). Acquisition of mass spectrometric data was performed in multiple reaction monitoring mode (MRM) in positive electrospray ionization using the transitions of m/z 104 --> 69 for GABA and m/z 106 --> 71 for d2-GABA. The method was linear in the concentration range of 5.00 to 1 000 ng x mL(-1). The intra- and inter-day precisions were within 9.9%, and accuracy ranged from 99.1% to 104%, within the acceptable limit across all concentrations. The method was successfully applied to a pharmacokinetic study of GABA tablets in healthy Chinese volunteers.
Chromatography, Liquid ; Humans ; Tandem Mass Spectrometry ; gamma-Aminobutyric Acid ; blood

A chiral LC-MS/MS method for the simultaneous analysis of desvenlafaxine (DVS) enantiomers in human plasma was developed and applied to a pharmacokinetic study on 12 Chinese healthy volunteers. d6-Desvenlafaxine was used as internal standard (IS). Chromatographic separation was performed on the Astec Chirobiotic V chiral column (150 mm x 4.6 mm, 5 μm). The assay was linear over the concentration range of 0.500-150 ng x mL(-1) for both enantiomers (r2 > 0.99). The method was successfully applied to a stereoselective pharmacokinetic study of 100 mg desvenlafaxine sustained release tablets on 12 Chinese healthy volunteers under fasting conditions. The results showed that the pharmacokinetic parameters were similar to both enantiomers in Chinese healthy volunteers. The AUC(0-t), and C(max) of the two enantiomers were about 1.5 times higher than those of blacks and whites reported in the literature.
Administration, Oral ; Area Under Curve ; Asian Continental Ancestry Group ; Chromatography, Liquid ; Cyclohexanols ; blood ; pharmacokinetics ; Delayed-Action Preparations ; Desvenlafaxine Succinate ; Dose-Response Relationship, Drug ; Healthy Volunteers ; Humans ; Male ; Plasma ; chemistry ; Stereoisomerism ; Tablets ; Tandem Mass Spectrometry

Objective To investigate the myocardial protective effects of“integrated strategy”with HOE-642 plus modified K/Mg on canine heart grafts.Methods Sixteen donors-recipient pairs of adult canines were divided into the“integrated strategy”group,i.e.,donor hearts were protected with HOE-642 plus K/Mg(IS,n=8)and the routine method(RM,n=8)group.Both groups un- derwent hypothermia stored for 4 h,followed by orthotopic transplantation.Cardiac heamodynamics was measured and myocardial ultrastructure and myocardial water content were evaluated.Results One of 8 animal died of aortic anastomoses leakage in each group,and the rest could wean from car- diopulmonary bypass successfully.Preservation of left ventricular contractility,as well as left ventric- ular compliance was significantly better in the IS group than in the RM group(P＜0.05),also,per- centage of myocardial water content was significantly lower in the IS group than in the RM group(P＜0.05).Myocardial ultrastructures were not damaged significantly in both groups,however,better myocardial preservation were seen in the IS group.Conclusion Both the clinically used“routine meth- od”and“integrated strategy”might provide safe donor heart preservation for 4 h,but the later scheme conferred more optimal effects with alleviating the myocardial swelling,preserving myocardial ultra- structure integrity and enhancing postischemic-reperfusion cardiac functional recovery.

This study is to establish physiologically based pharmacokinetic (PBPK) models of famitinib in rat and monkey, and then to predict the pharmacokinetics and tissue distribution of famitinib in human based on the PBPK models. According to published paper, previous studies and the chemical properties of famitinib predicted by ACD/ADME suite and SimCYP, the PBPK models of rat and monkey were established and optimized using GastroPlus. And then, the PBPK models were applied to predict the pharmacokinetic and tissue distribution of famitinib in human. The results showed that the PBPK models of rat and monkey can fit the observed data well, and the AUC0-∞, ratios of observed and calculated data in rat and monkey were 1.00 and 0.97, respectively. The AUC0-∞, ratios of observed and predicted data in human were 1.63 (rat to human) and 1.57 (monkey to human), respectively. The rat and monkey PBPK models of famitinib were well established, and the PBPK models were applied in predicting pharmacokinetic of famitinib in human successfully. Hence, the PBPK model of famitinib in human could be applied in future drug-drug interaction study.
Animals ; Antineoplastic Agents ; pharmacokinetics ; Haplorhini ; Humans ; Indoles ; pharmacokinetics ; Models, Biological ; Pyrroles ; pharmacokinetics ; Rats ; Receptor Protein-Tyrosine Kinases ; antagonists & inhibitors ; pharmacokinetics ; Tissue Distribution