Objective To investigate the effect of early postoperative enteral nutrition support on the balance of free amino acid spectrum in plasma for patients with cardiac valve replacement during perioperative period. Methods (Forty-seven) patients undergoing cardiac valve replacement were divided into two groups randomly, the routine diet group and the Nutrison Fibre group. The levels of free amino acids in plasma were measured with pre-column derivatization of high-performance liquid chromatography. Results During perioperative period most free amino acids in plasma decreased significantly in the routine diet group (Plt;0.05). Despite some free amino acids in plasma decreased significantly in the Nutrison Fibre group(Plt;0.05), all free amino acids in plasma returned to (Pgt;05) or were higher than the preoperative levels in the postoperative sixth day (Plt;0.05). At the same postoperative points, most free amino acids in plasma in the Nutrison Fibre group were higher than that of the routine diet group (Plt;0.05). Conclusions The levels of free amino acids in plasma decrease significantly in patients with cardiac valve replacement after operation. Early postoperative Nutrison Fibre enteral nutrition support is helpful for keeping the balance of free amino acids in plasma for patients with cardiac valve replacement.
Objective To compare the systematic and lung pharmacokinetic parameters of moxifloxacin hydrochloride and explore a feasible tool to monitor drug concentration and evaluate therapeutic efficacy of respiratory fluoroquinolones. Methods Ten adult patients with community-acquired pneumonia or acute exacerbation of chronic bronchitis were enrolled.The subjects received a single dose of oral moxifloxacin hydrochloride 400 mg. Serum specimens were sampled at 0，1，2，3，4，8，24 h and sputum specimens were collected 0，1，2，4，8，20，24 h after administration，respectively.The serum and sputum concentrations of moxifloxacin hydrochloride were assayed by means of high-performance liquid chromatography. Standard pharmacokinetic parameters including peak concentrations(Cmax) and area under the concentration-time curve (AUC0-24 h) were assessed. Results Serum C(max) was（5.95±1.35）mg/L at 2 hours and serum AUC0-24 h was (58.72±8.11）mg·h-1·L-1 while sputum Cmax and AUC0-24 h were （16.18±6.47）mg/L at 3 hours and （138.04±78.29）mg·h-1·L-1 respectively，which were significantly higher than those in serum. Conclusion Oral administration of moxifloxacin hydrochloride to patients with respiratory infections results in rapid penetration into lung and maintain a one-fold drug concentration compared to blood concentration within 24 hours.Sputum drug concentration analysis demonstrates a superior pharmacokinetic profile of moxifloxacin in respiratory tract.
ObjectiveTo study the pharmacokinetics of lovastatin/niacin sustained-release tablets in healthy Chinese volunteers. MethodsEligible subjects were enrolled to receive a single dose of 20/500, 20/750 and 20/1 000 mg lovastatin/niacin sustained-release tablets and multiple dose of 20/1 000 mg lovastatin/niacin sustainedrelease tablets, one time per day, sustained for 5 days, respectively. Blood samples were obtained before dosing and up to 10, 20, 30, and 45 minutes, and 1 hour, 1.5, 2, 2.5, 3, 3.5, 4, 5, 7, 9, 12, and 15 hours after dosing. Niacin, niacinamide, nicotinuric acid and lovastatin were detected by high performance liquid chromatography-tandem mass spectrometry method. ResultsThe peak concertration and the area under the plasma concentration-time curve (0-t) of nicotinuric acid had linear dynamics characteristics with the dosage when the dose of niacin was between 500 and 1 000 mg. After multiple dosing, pharmacokinetics parameters of nicotinuric acid and lovastatin were close. No significant diTherence was found between male and female subjects. ConclusionLovastatin/niacin sustained-release tablets possess linear kinetics. Accumulation is not significant after multiple dosing. Gender doesn't affect the pharmacokinetics parameters.
ObjectiveTo establish an accurate and sensitive high performance liquid chromatography-mass spectrometric (HPLC/MS/MS) method for determination of vorinostat (SHA) and M2 metabolites in human serum, which was applicable for pharmacokinetic study of SHA. MethodsThe essay was conducted with an API 3000 HPLC-MS/MS system consisted of a Gemini C18 column (50 mm×3 mm, 3 μm), and the mobile phase consisted of methanol-acetonitrile-water-1 mol/L NH3-formic acid (25:15:60:0.1:0.05) at a flow rate of 0.23 mL/min. Acidulated serum samples were extracted by 3.5 mL diethyl ether which contains 3% isopropyl alcohol and was operated under the multiple reaction monitoring mode using the electrospray ionization technique. d5-SHA was used as the internal standard. ResultsThe retention time of SHA, M2 metabolite and internal standard were 4.1, 3.1 and 4.0 minutes, respectively. The linear range of SHA and M2 metabolite were in the range of 1-1 000 and 2-2 000 ng/mL, and the limit of quantity were 1.0 and 2.0 ng/mL; the method recovery were 93.0%-99.3% and 88.11%-104.12%, respectively. Matrixes effect of SHA and M2 metabolite were blow 9.0%. ConclusionThis method for the quantitative determination of SHA and M2 in human serum was proved to be simple, rapid, sensitive and accurate; it can be applied in the determination of SHA and M2 metabolite.
ObjectiveTo evaluate the reasonableness of anticoagulation management strategy in patients after mechanical heart valve replacement. MethodsAll patients were followed and registered continually at outpatient clinic from July 2011 to February 2013, with a minimum of 6 months after surgery. Targeted international normalized rate (INR) 1.60 to 2.20 and warfarin weekly dosage adjustment were used as the strategy of anticoagulation management. Except bleeding, thrombogenesis and thromboembolism, time in therapeutic range (TTR) and fraction of TTR (FTTR) were adopted to evaluate the quality of anticoagulation management. ResultsA total 1 442 patients and 6 461 INR values were included for data analysis. The patients had a mean age of 48.2±10.6 years (14-80 years) and the following up time were 6 to 180 months (39.2±37.4 months) after surgery. Of these patients, 1 043 (72.3%) was female and 399 (27.7%) was male. INR values varied from 0.90-8.39 (1.85±0.49) and required weekly doses of warfarin were 2.50-61.25 (20.89±6.93 mg). TTR of target INR and acceptable INR were 51.1% (156 640.5 days/306 415.0 days), 64.9% (198 856.0 days/306 415.0 days), respectively. FTTR of target INR and acceptable INR were 49.4% (3 193 times/6 461 times), 62.6% (4 047 times/6 461 times). There were 8 major bleeding events, 7 mild bleeding events, 2 thromboembolism events, and 2 thrombogenesis in the left atrium. ConclusionIt is reasonable to use target INR 1.60-2.20 and warfarin weekly dosage adjustment for patients after mechanical heart valve replacement.
ObjectiveTo study the tolerance of Ice Gardenia Pain Aerosol with single and multiple dosing in healthy Chinese volunteers, evaluate the safe dosing range and the highest tolerance dose of human body, and supply proof for the dose amount in Phase-Ⅱ study. MethodsForty subjects enrolled in Ward I of a national medicine clinical experiment institute between May and September 2014 were included in this study. For single dosing experiment, 28 eligible subjects were enrolled and assigned into 5 groups to receive a single dose of 2, 6, 10, 14 and 18 puffs per time, respectively. The patient number for each group was 4, 6, 6, 6 and 6, respectively with equal number of male and female patients in each group. For the multiple dosing treatment, 12 eligible subjects were enrolled and assigned into 2 groups to receive multiple dosing of 6 and 10 puffs per time per day, respectively, for 14 days. Both the two groups had 6 male and female patients. Tolerability was evaluated by monitoring adverse events, physical examinations, laboratory tests and electrocardiogram. ResultsTotally, 40 subjects were enrolled and all of them completed the study. No adverse events or severe adverse events were observed or reported. No abnormal laboratory test was reported 1 hour, 2, 4, 8, 12 and 24 hours after the treatment of single dosing, and multiple dosing group had no abnormal indexes or adverse events, either. The maximum single tolerance dose was 18 puffs per time, and a single dose of 2-18 puffs per time was well tolerated; Multiple dosing of 6 and 10 puffs per day, once a day for 14 days was well tolerated. ConclusionsSingle and multiple dosing of Ice Gardenia Pain Aerosol are considered to be well tolerated by healthy Chinese volunteers. The maximum single tolerance dose is 18 puffs per time; multiple dosing of 6 and 10 puffs per day, once a day for 14 days is well tolerated. We suggest that the above dosing range can be chosen in the following Phase-Ⅱ study.
目的 采用高效液相色谱-质谱联用法研究盐酸多奈哌齐口腔崩解片的人体药物代谢动力学，并评价其生物等效性。 方法 2009年9月－11月对22例健康男性受试志愿者单次交叉口服盐酸多奈哌齐口腔崩解片（试验制剂）和盐酸多奈哌齐普通片（参比制剂），测定给药后不同时间点血浆中多奈哌齐经时血药浓度，采用DAS 2.0软件进行药物代谢动力学参数计算和生物等效性评价。 结果 受试者单次口服试验制剂与参比制剂后，达峰时间分别为（2.95 ± 1.16）、（3.19 ± 0.98） h，峰浓度分别为（9.98 ± 2.93）、（9.13 ± 2.05） ng/mL，药时曲线下面积（0-t）分别为（470.76± 142.64）、（446.57 ± 137.30）ng/mL·h；药时曲线下面积（0-∞）分别为（517.74 ± 169.79）、（489.47 ± 162.13）ng/mL·h。试验制剂与参比制剂的生物等效性结果为104.7%，其90%置信区间为（98.4%，111.4%）。结论 盐酸多奈哌齐口腔崩解片与普通片生物等效。
目的 研究高效液相色谱-质谱联用法（HPLC-MS/MS）测定血浆中二亚油酰磷脂酰胆碱（DLPC）浓度测定的方法。 方法 2010年11月－2011年1月，7例受试者，3例服用多烯磷脂酰胆碱软胶囊（试验制剂），3例服用多烯磷脂酰胆碱胶囊（参比制剂），1例未服药；采集服药者血浆，对各种检测方法、样品预处理条件进行考核；用建立的方法对6例服药者和1例未服药者血浆DLPC浓度进行测定。 结果 最终建立的方法为：采用API 3000型HPLC-MS/MS液质联用系统，多反应离子检测模式，正离子扫描，大气压化学电离源，色谱柱为Ultimate CN分析柱（50.0 mm × 4.6 mm，5 ?m），流动相为甲醇︰水︰甲酸（80︰20︰0.05，V/V/V），流速为0.5 mL/min，格列齐特作为内标。受试者口服多烯磷脂酰胆碱软胶囊试验制剂与参比制剂后，DLPC血浆浓度水平均未见明显的变化规律。未服药者血浆DLPC浓度也有较高浓度水平。 结论 所建立的HPLC-MS/MS法，未能用于多烯磷脂酰胆碱软胶囊生物等效性评价。
目的 采用高效液相色谱法测定受试者口服埃索美拉唑肠溶胶囊与埃索美拉唑镁肠溶片后血药浓度，评价埃索美拉唑肠溶胶囊的生物等效性。 方法 2009年9月－10月，36例健康男性受试者单次交叉口服埃索美拉唑肠溶胶囊（试验制剂）和埃索美拉唑镁肠溶片（参比制剂），测定给药后不同时间点血浆中埃索美拉唑经时血药浓度，采用DAS 2.0软件进行药物代谢动力学参数计算和生物等效性评价。 结果 受试者单次口服试验制剂与参比制剂后，达峰时间分别为（2.19 ± 0.96）、（2.43 ± 0.92） h，峰浓度分别为（1 748.86 ± 615.81）、（1 442.92 ± 476.41） μg/L，药时曲线下面积（AUC）0-t分别为（3 927.14 ± 1 839.10）、（3 878.79 ± 1 734.84） μg/L·h，AUC0-∞分别为（3 998.36 ± 1 866.22）、（3 918.31 ± 1 773.44） μg/L·h。试验制剂与参比制剂的生物等效性为94.0%，其90%CI为（82.3%，107.2%）。 结论 埃索美拉唑肠溶胶囊与埃索美拉唑镁肠溶片生物等效。