Heart Failure ; therapy ; Humans

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

Objective To investigate the morbidity,clinical feature,diagnosis and therapy of ovarian disease in children.Methods Eighty-two children with ovarian disease were admitted and treated in Nanjing children's hospital from Jan.1992 to Jan.2007,were analyzed retrospectively with age,emergency admissions or not,dwell,pathology and method of operation.Results The age of 82 patients ranged from 1 day to 14 years old and the mean age was 6.7 years old.Thirty-one cases(37.8%) were emergency admissions and 51 cases(62.2%) were routine admissions.Twenty-seven cases(32.9%) were rural patients and 55 cases(67.1%) were urban patients.Forty-five cases(54.8%) were nontumorous disorder,31 cases(37.8%) were benign tumor and only 6 cases(7.4%) were malignant tumor.About the morbidity,12 patients(14.6%)were admitted from 1992 to 1996,24 patients(29.5%) from 1997 to 2001 and 46 patients(55.9%) from 2002 to 2007.Chemotherapy were carried out in 6 cases with malignant tumor in internal medicine,2 cases with sexual precosity kept observation,the others were cured.Conclusions Ovarian disease can occur at any age in children.The clinical manifestation is characterized mainly by acute abdomen.The incidence of ovarian disease of children in urban areas is higher than that children in rural areas.The morbidity continues to show an upward tendency and the pathologic manifestations are mostly benign,laparoscopic operation has obviously superiority.

To study the metabolite excretion of theophylline, a rapid and specific method by liquid chromatography with heated electrospray ionization tandem mass spectrometry (LC-HESI/MS/MS) method for simultaneous determination of theophylline, 1, 3-dimethyluric acid (1,3-DMU), 3-methylxanthine (3-MX) and 1-methyluric acid (1-MU) in human urine was developed using theophylline-d6 and 5-fluorouracil as internal standards. Selected reaction monitoring (SRM) with heated electrospray ionization (HESI) was used in the negative mode for mass spectrometric detection. After diluted with methanol and centrifuged, the analytes and ISs were separated on a XDB-Phenyl (150 mm x 4.6 mm, 5 microm) column with a mixture of water-methanol-formic acid (30 : 70 : 0.15) as mobile phase at a flow rate of 0.6 mL x min(-1). The linear calibration curves for theophylline, 1, 3-DMU, 3-MX and 1-MU were obtained in the concentration range of 1.0-250 microg x mL(-1), separately. The method herein described is effective and convenient, and can be used for determination of theophylline and its three metabolites. The results showed that urinary excretion ratio of theophylline, 1,3-DMU, 3-MX and 1-MU is approximately 1 : 3 : 1 : 2 in Chinese subjects, which is similar to the reported excretion pattern in Caucasian.
Administration, Oral ; Asian Continental Ancestry Group ; Calibration ; Chromatography, Liquid ; Delayed-Action Preparations ; metabolism ; Healthy Volunteers ; Humans ; Spectrometry, Mass, Electrospray Ionization ; Tablets ; Tandem Mass Spectrometry ; Theophylline ; metabolism ; urine ; Uric Acid ; analogs & derivatives ; urine ; Xanthines ; urine

OBJECTIVETo elucidate whether the plasma concentration of NT-proBNP in patients with acute coronary syndrome (ACS) correlated with severity of the diseases and whether NT-proBNP is a reliable biochemical marker correctly indicates the severity of ACS.

METHODSEighty-nine subjects came from CCU of Cardiology Department of People's Hospital Beijing University from October 2003 to June 2004 and aged 34-85 y (66.89 +/- 11.12 y). In this study the spectrum of ACS only included unstable angina pectoris (UA) and acute myocardial infarction (AMI). Patients with UA were separated into 3 groups by Braunwald classes and those with AMI were separated into 4 groups by Killip classes when their venous blood samples were collected. Plasma concentration of NT-proBNP was measured by enzyme linked immunoabsorbent assay. Data was estimated by SPSS.

RESULTSThe concentration of NT-proBNP in patients with ACS was dramatically correlative with the severity of the diseases: with the upgrading of Braunwald classes, the concentration of NT-proBNP in patients with UA increased gradually; in patients with AMI it also raised gradually with the upgrading of killip classes; furthermore, the plasma concentration of NT-proBNP in patients with AIM increased much more than that in patients with UA when they are at the similar NYHA functional class.

CONCLUSIONPlasma concentration of NT-proBNP in patients with ACS might be a reliable biochemical marker which can objectively indicate the degree of this diseases.

Acute Coronary Syndrome ; blood ; physiopathology ; Adult ; Aged ; Aged, 80 and over ; Humans ; Middle Aged ; Natriuretic Peptide, Brain ; blood ; Peptide Fragments ; 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 analyze and summarize the features of children's facial wound and to share the emergency treatment experiences.Methods An retrospective study was conducted on the pathogenesis,age distribution,emergency treatment methods and complications in 1407 children (under 15 years of age) during recent 8 years (from January 2004 to December 2011).Results In this study the major facial wound type was simply lacerations (1196/1407,85.0 ％),and the most common wound cause was trumbling injury (1154/1407,82.0 ％).The T area was the easiest injured,successively,forehead (562/1407,39.9％),chin (211/1407,15.0％),lips (196/1407,13.9％) and nose (95/1407,6.8％).Here were 2 peaks in age distribution which were 2 and 5 years of age,respectively.Pleased outcome would be found while normalized plastic means were taken.After 3 to 6 months following up,there were 5 infection cases,27 cases healed with hypertrophic scars,and 7 cases with traumatic tattoos in wound location.Conclusions The most common wound type is simply laceration.2 and 5 years of age are two of the highest risk stages.It is necessary to act up to plastic surgery principles and take children's particularity into account when emergency treatment,and to do our best to minimize the scar in the first operation time.

Objective To search for a good solution for aesthetic beard reconstruction and to explore the effect of the single-hair grafting in beard reconstruction. Methods Under the local anesthesia, a scalp strip (length range from 5～7 cm, width range from 1.0～1.5 cm) was harvested from the back of the head and then was divided into a series of single-hair micrografts. After the slits were made, the grafts were implanted into the holes, parallel to the original beard directions. The donor sites were directly closed. With this method, 18 sparse beard patients and 3 patients with upper lip scars were treated. Results The grafted hairs grew nearly in the direction of normal beard, which achieved 90 %～95 % survival in recipient areas. The patients were satisfied with the results, in which 19 cases received only 1 operation and 2 cases received another repeated operation. Conclusion Beard reconstruction by single-hair grafting technique is a good, safe and effective method.

AIMTo investigate the impact of CYP2C9 * 3 on the pharmacokinetics of glibenclamide and lornoxicam.

METHODSCYP2C9 * 3 was measured in 83 non-related Chinese subjects by PCR-RFLP. The pharmacokinetics of lornoxicam and glibenclamide were investigated in 18 subjects (7 with CYP2C9 * 1/* 3 genotype and 11 with * 1/* 1 genotype). Glibenclamide and lornoxicam in plasma were determined by the sensitive liquid chromatography-tandem mass spectrometry, separately.

RESULTSAfter a single oral dose of 2.5 mg glibenclamide, C(max) was (70.0 +/- 11.5) microg x L(-1) in CYP2C9 * 1/ * 3 subjects and (51.9 +/- 12.3) microg x L(-1) in * 1/ *1 subjects. AUC(0-infinity) were (435 +/- 47) vs (287 +/- 95) microg x h x L(-1) (in * 1/ * 3 vs * 1/ *1 subjects), and CL/F were (96 +/- 9.3) vs (160 +/- 51) mL x min(-1), respectively. Statistic analysis results indicated that glibenclamide AUC(0-infinity) was significantly higher (1.5-fold) and subsequently CL/F was significantly lower (40%) in CYP2C9 * 1/ * 3 subjects than those in * 1/ * 1 subjects (P < 0.01). After a single oral dose of 8 mg lornoxicam, C(max) was (1.54 +/- 0.24) mg x L(-1) in CYP2C9 * 1/ * 3 subjects and (1.19 +/- 0.37) mg x L(-1) in * 1/ * 1 subjects. AUC(o-infinity were (14.9 +/- 2.2) vs (6.92 +/- 1.48) mg x h x L(-1) (in * 1/ *3 vs * 1/ * 1 subjects), and CL/F were (9.1 +/- 1.2) vs (20.1 +/- 4.6) mL x min(-1), respectively. Statistic analysis results indicated that lornoxicam AUC(0-infinity) was significantly higher (2. 2-fold) and subsequently CL/F was significantly lower (55% ) in CYP2C9 * 1/ * 3 subjects than those in * 1/ * 1 subjects (P < 0.001).

CONCLUSIONCYP2C9 * 3 greatly affects both the pharmacokinetic profiles of glibenclamide and lornoxicam. The elimination of these drugs significantly decreased in subjects with CYP2C9 * 1/ * 3 genotype, especially lornoxicam.

Adult ; Alleles ; Anti-Inflammatory Agents, Non-Steroidal ; pharmacokinetics ; Area Under Curve ; Aryl Hydrocarbon Hydroxylases ; genetics ; Asian Continental Ancestry Group ; China ; Cytochrome P-450 CYP2C9 ; Genotype ; Glyburide ; pharmacokinetics ; Humans ; Hypoglycemic Agents ; pharmacokinetics ; Male ; Piroxicam ; analogs & derivatives ; pharmacokinetics ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length

This study aims to develop a liquid chromatography with tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of ivabradine and N-demethylivabradine in human plasma, and investigate effects of stable isotope labeled (SIL) internal standard (IS) on ivabradine. The analytes and IS were extracted from plasma by protein precipitation with acetonitrile, and chromatographied on a Capcell PAK C18 (100 mm x 4.6 mm, 5 μm) column using a mobile phase of methanol and 5 mmol x L(-1) ammonium acetate. Multiple reaction monitoring with electrospray ionization (ESI) was used in the positive mode for mass spectrometric detection. The effect of ivabradine isotope peak [M+H+3] + on IS and the effect of SIL IS purity on ivabradine were evaluated. An appropriate concentration of SIL IS was chosen to permit method selectivity and linearity of the assay over the required range. The standard curves were demonstrated to be linear in the range of 0.100 to 60.0 ng x mL(-1) for ivabradine, and 0.050 0 to 20.0 ng x mL(-1) for N-demethylivabradine. The intra and inter day precision and accuracy were within the acceptable limits for all concentrations. Besides, the interaction between IS and ivabradine did not impact the determination of analytes. This method was successfully applied to a pharmacokinetic study of hydrogen sulfate ivabradine sustained release tablets on Chinese healthy volunteers.
Benzazepines ; blood ; Chromatography, High Pressure Liquid ; Delayed-Action Preparations ; Humans ; Isotope Labeling ; standards ; Reference Standards ; Reproducibility of Results ; Sensitivity and Specificity ; Spectrometry, Mass, Electrospray Ionization ; Tablets ; Tandem Mass Spectrometry