雷诺嗪缓释片在比格犬体内的药代动力学

目的:研究雷诺嗪缓释片在比格犬体内的药物代谢动力学,并与参照制剂比较,为其是否具有缓释特征提供依据。方法:首先建立血浆中雷诺嗪浓度的液相色谱-串联质谱联用检测方法,并考察方法的专属性、准确度、日内日间精密度、回收率、线性范围等。采用随机对照试验设计,将12只比格犬随机分为A、B组,每组6只,分别服用1片雷诺嗪缓释片(500 mg/片)和1片参比制剂雷诺嗪片(500 mg/片),均于给药前和给药后不同时间点采集血样,用已建立的液质联用方法检测血样中雷诺嗪的血药浓度,计算2组比格犬的药代动力学参数。结果:受试组和参照组半衰期t1/2分别为13.3±8.3和2.36±0.92 h,峰浓度Cmax分别为923.9±340.5和3205±1314 ng/mL,达峰时间Tmax分别为1.6±0.38和0.88±0.14 h,曲线下面积AUC0~∞分别为6252.1±2860.3和9916±4305(ng·h)/mL,清除率Cl分别为11.3±9.8和6.39±3.95 L/(kg·h)。受试制剂雷诺嗪缓释片和参比制剂雷诺嗪片的药代特征和血药浓度-时间变化趋势明显不同,受试组血药浓度缓慢上升和下降,峰值较低;而参照组血药浓度峰值显著高于受试组,有明显的突释效应。结论:液质联用检测方法准确可靠,适合体内药代动力学研究;与参比制剂雷诺嗪片相比,受试制剂雷诺嗪缓释片符合缓释片的基本药代动力学特点。     

辛伐他汀自微乳化胶囊的体内评价

目的:研究辛伐他汀(SV)自微乳化胶囊在比格犬体内的药代动力学。方法:采用HPLC法测定比格犬血浆药物浓度,与市售片比较,考察SV自微乳化胶囊的体内药代动力学。结果:药代动力学测定结果表明:与市售片比较,自微乳化胶囊血药浓度达峰时间提前、最高血药浓度增大,Tmax=1.41h,Cmax=46.22ng.mL-1,而市售片的Tmax=2.65h,Cmax=12.43ng.mL-1;AUC0-∞为市售片剂的227.5%。结论:自微乳化胶囊可以显著提高SV的体内吸收。     

RP-HPLC法测定阿托伐他汀在新西兰兔体内的药代动力学

目的:研究阿托伐他汀片在新西兰兔体内的药代动力学.方法:18只成年健康雄性新西兰兔.随机分为正常对照组、10mg/kg·d阿托伐他汀片组与15 mg/kg·d阿托伐他汀片组,每组6只,采用RP-HPLC法测定血药浓度,计算药代动力学参数.结果:10mg/kg·d组与15 mg/kg·d组的主要药代动力学参数分别为:AUC0～t/μ g·L-1·h为(619.58±215.45)与(1138.34±422.32)、AUC0～∞/μ g·L-1·h为(655.68±242.83)与(1216.57±353.64)、Cmax/μ g·L-1为(455.81±168.52)和(896.53±168.5.8)、MRT0～t/h为(3.68±0.75)与(5.73±0.56)、MRT0～∞/h为(3.83±0.91)与(5.25±0.48)、Tmax/h为(2.51±0.82)与(3.68±0.33)、T1/2/h为(4.22±0.55)与(9.51±0.67).结论:RP-HPLC法适用于阿托伐他汀片动物药代动力学的研究.     

RP-HPLC法测定银黄冲剂中黄芩苷在大鼠体内的血药浓度及药代动力学研究

采用高效液相色谱法测定银黄冲剂中黄芩苷在大鼠血浆中的浓度,并研究其药代动力学。色谱柱为D iamonsilTMC18(250 mm×4.6 mm,5μm)柱,流动相:甲醇-磷酸二氢钠缓冲液(pH 2.6),体积比为52:48,检测波长275 nm,流速:1.0 mL/m in。结果血浆中黄芩苷在0.05~20μg/mL范围呈良好的线性关系,r2=0.9997,最低定量限为6 ng/mL。大鼠按1.6 g/kg灌胃银黄冲剂后,黄芩苷的血药浓度时间曲线符合口服吸收有滞后时间的二房室模型,主要药动学参数为t1/2:0.17 h,Vd:2.65 L,K12:5.36/h,K21:0.71/h,Ke:4.25/h,AUC:2.01μg.h/mL。HPLC测定黄芩苷的血药浓度操作便捷,灵敏度高,适用于黄芩苷的药代动力学研究。     

辛伐他汀在大鼠体内药动学性别差异的研究

目的:研究Wistar大鼠单次灌服辛伐他汀后体内药代动力学的性别差异。方法:利用高效液相色谱方法检测大鼠血浆中辛伐他汀浓度,采用非房室模型法计算各自药动学参数。结果:雌、雄大鼠体内Cmax分别为(144.66±22.31)ng·mL~(-1)和(165.91±52.50)ng·mL~(-1);t_(1/2)分别为(4.74±1.19)h和(14.98±6.64)h;AUC_(0-10)分别为(0.990±0.19)μg.h·mL~(-1)和(0.726±0.15)μg·h·mL~(-1);AUC0-∞分别为(1.62±0.47)μg·h·mL~(-1)和(2.19±0.62)μg·h·mL~(-1);MRT分别为(9.69±1.60)h和(23.08±8.89)h,经t-检验,雌、雄大鼠主要药动学参数t_(1/2)、AUC_(0-10)、MRT均有统计学显著性差异(p<0.01)。结论:辛伐他汀在大鼠体内的药代动力学存在明显的性别差异,辛伐他汀在雌性大鼠体内代谢较快。     

不同成熟期栀子果实有效成分累积的研究

根据果实颜色可以将栀子成熟期划分为全青期、2/3青1/3黄期、半青半黄期、1/3青2/3黄期、全黄期、枯黄期.采用HPLC法测定栀子果实在不同成熟时期3种主要有效成分栀子苷、绿原酸、西红花苷-1的含量.结果表明:栀子苷、绿原酸、西红花苷-1含量均出现两个高峰期,峰形陡峭;高峰出现的时期不完全一致.栀子苷的含量在全青期和1/3青2/3黄期最高,而西红花苷-1的含量在全青期和全黄期最高.全青期为栀子苷和西红花苷-1的最佳采收期.根据果实颜色及时采收才能获得高含量的目标活性成分.     

硫柳汞SD 大鼠单次静脉注射药代动力学研究

目的:研究硫柳汞在SD大鼠静脉注射后的药代动力学特征。方法:SD大鼠单剂量(高、低2个剂量组)静脉注射硫柳汞,以冷原子吸收测汞法测定不同时间点的血药浓度,用DAS2.0软件获取各剂量组的主要药代动力学参数。结果:硫柳汞在高(30mg/kg)和低剂量(15 mg/kg)的消除半衰期t1/2z分别为171.61±0.33h,,156.54±18.61h;AUC0-144h分别为16748.65±7296.61mg/L*h,9131.94±1406.68 mg/L*h。结论:硫柳汞在大鼠体内的代谢过程呈线性动力学特征,半衰期约在130～170h左右。     

栀子果实成熟度对栀子苷含量积累的影响

目的:考察栀子果实成熟度与栀子苷含量积累的关系,为确定最适采收期奠定基础。方法:以不同成熟度的栀子果实为样品,采用高效液相色谱法测定栀子苷含量,并进行对比。结果:6个不同成熟度果实样品的栀子苷含量随成熟度提高而下降,果实全青渐变色时栀子苷含量最高(8.469%);在果实3/4红前含量下降缓慢(-3.71%),差异不明显;果实全红后含量下降显著(-12.18%～32.55%)。结论:药用栀子果实的采摘应以果实全青渐变到果实3/4红前及时采摘。     

高速逆流色谱分离制备栀子苷

以栀子苷粗提取物为原料,采用高速逆流色谱法分离栀子苷,溶剂系统为A:乙酸乙酯∶正丁醇∶水(2∶1.5∶3)和B∶正丁醇∶水(1∶1),上相为固定相,下相为流动相,流速为2.0 mL/min,转速为850 r/min,温度控制在25℃,纯度用HPLC测定.结果表明,利用溶剂系统A和B进行HSCCC制备栀子苷,使栀子苷含量从50.75％(HPLC)分别提高至86.6％和91.8％,回收率分别为81.36％和78.12％.     

黄芪甲苷在大鼠体内的药代动力学和组织分布研究

建立了固相萃取-HPLC-MS测定大鼠血浆中黄芪甲苷含量的方法,并对其在大鼠体内的药代动力学和组织分布进行了研究。分别以1,2,4 mg/kg的剂量对大鼠静脉给药,给药后2,10,20,30,60 min和1.5,2,3,4,6,8 h采集血样,同时以2 mg/kg的剂量对大鼠静脉给药,给药后20,60,240 min采集各组织,测定血浆样品和组织样品中的黄芪甲苷浓度。血药浓度-时间曲线按二室模型拟合最佳,t1/2(α)分别为12.36,7.05,15.98 min,t1/2(β)分别为69.14,73.28,95.24 min,AUC分别为277.36,415.36,623.15μg.min/mL,AUC与剂量的线性方程为y=113.64x 173.47(r=0.997),表明黄芪甲苷在大鼠体内呈线性消除。组织分布研究表明黄芪甲苷在体内分布较广。     

血清C反应蛋白、正五聚蛋白-3对小儿肺动脉高压的诊断价值

目的:研究血清C反应蛋白(CRP)和正五聚蛋白-3(PTX-3)在小儿肺动脉高压(PAH)诊断中的临床价值。方法:选择32例PAH患儿及32例健康小儿,检测和比较其血清CRP、PTX-3水平,分析血清CRP、PTX-3水平的相关性,通过绘制ROC曲线评价其对于PAH的诊断价值。结果:PAH组血清CRP水平(29.63±15.82 mg/L)、PTX-3水平(1.20±1.03 ng/m L)与对照组[CRP水平(3.38±1.74 mg/L)、PTX-3水平(0.64±0.43 ng/m L)]相比均显著升高(P0.01)。血清CRP与PTX-3的相关系数r为0.356(P0.05)。血清CRP诊断PAH的ROC曲线AUC为0.983,临界点为6.6 mg/L;PTX-3诊断PAH的ROC曲线AUC为0.669,临界点为0.95ng/m L;两者联合诊断的AUC为0.986,临界点为1.01。结论:PAH患儿血清PTX-3和CRP水平均显著升高,CRP大于PTX对PAH的诊断价值,两者联合诊断的价值更大。     

tBHQ和SFN在创伤性脑损伤小鼠中的疗效比较性分析

目的:探讨叔丁基对苯二酚(t BHQ)和莱菔硫烷(SFN)在患有创伤性脑损伤大鼠的疗效差异性。方法:80只健康成年的雄性SD大鼠分为假手术组、常规损伤组、t BHQ治疗组和SFN治疗组,使用电子颅脑损伤仪(e CCI)制备TBI模型。其中t BHQ治疗组在伤前24 h大鼠腹腔注射三次t BHQ(50 mg/kg),每8 h一次;SFN治疗组在伤后15 min给予腹腔注射SFN(5 mg/kg)。给药24 h后,采用m NSS方法评价各组大鼠神经功能缺损状况,利用干湿称量法计算脑含水量,Western blot和ELISA方法分别测定大鼠脑组织的NOX2和Nrf2的表达水平。结果:损伤发生后第24 h,t BHQ治疗组和SFN治疗组在m NSS评分((4.5±0.71)vs(9.2±0.79),(6.0±0.82)vs(9.2±0.79))、脑水肿(79.4%vs 85.6%,80.3%vs 85.6%)、NOX2和Nrf2(0.93 ng/m L vs 0.81 ng/m L,0.87 ng/m L vs 0.81 ng/m L)表达上与常规损伤组差异明显,而t BHQ治疗组和SFN治疗组间在m NSS评分((4.5±0.71)vs(6.0±0.82))、NOX2和Nrf2(0.93 ng/m L vs 0.87 ng/m L)表达上差异显著。结论:在大鼠TBI模型中,t BHQ和SFN均可以有效的降低机体自身的氧化应激作用,并改善神经功能,但t BHQ的疗效要好于SFN。     

Chromium intake and urinary chromium excretion of trauma patients

Glucose metabolism is altered after trauma and those factors that affect glucose metabolism often affect chromium (Cr) metabolism and excretion. To ascertain whether urinary Cr excretion is affected by the elevated serum glucose and other factors associated with trauma, the serum glucose and urinary Cr and Creatinine (Cre) excretion of seven severely traumatized patients were determined. The Cr concentration of intravenous (IV) fluids administered was determined and approximate Cr intake calculated. For all patients, urinary Cr concentration was high in the initial sample collected within 24 h of admission (10.3 ± 2.5 ng/mL, mean ± SEM) and decreased significantly (P < 0.05) by 42 h (2.0 ±0.6 ng/mL). The mean urinary Cr concentration 42 h following admission was 10 times greater than the urinary Cr concentration of normal, healthy subjects (0.2 ± 0.02 ng/mL). There was no significant change in urinary Cre concentration within 42 h of admission, therefore the ratio of urinary Cr to Cre (ng Cr:mg Cre) also decreased. Serum glucose concentration was elevated at admission (170 ± 18 mg/dL, mean ± SD) and decreased to 145 ± 10 mg/dL by 48 h post-admission. The intravenous fluids, dextrose and NaCl, were the lowest in Cr of the samples tested, range 0.02 to 0.20 ng/mL; lactated Ringer’s solution, with or without dextrose, contained 10-20 times more Cr and plasma protein fraction contained approximately 32 ng/mL. The mean calculated Cr intake for the first 24 h postadmission was 37.1 µg/d, significantly greater (P < 0.01) than intake from 24 to 48 h (0.12 µg/d) and 48-72 h (1.63 µg/d). The IV intake of Cr varied for trauma patients depending on fluids required during treatment, but for all patients the relatively high IV Cr intake was rapidly excreted in the urine. These data demonstrate that urinary Cr concentration is elevated several-fold within 24 h of trauma and that Cr contents of intravenous fluids administered in the days immediately following injury vary dramatically. The effects of trauma alone on Cr excretion are difficult to assess because of the variable intake of Cr from IV fluids.     

替考拉宁在感染的血液病患者中血药浓度的监测与应用价值分析

目的:探讨替考拉宁在感染的血液病患者中血药浓度的监测与应用价值。方法:回顾分析2017年12月-2019年12月来我院治疗的42例革兰氏阳性球菌引起感染的血液病患者临床资料,按照临床替考拉宁的给药剂量分A组和B组,每组21例。利用高效液相色谱法(HPLC)检测患者第5天用药前30 min的血药浓度,利用酶联免疫荧光法检测患者降钙素原(PCT)水平。比较两组血药浓度,临床疗效及PCT水平的差异,并记录不良反应。结果:B组患者血药浓度(15.12±4.68)mg/L高于A组的(11.76±5.31)mg/L,且B组患者PCT水平(0.86±1.21)ng/mL低于A组的(2.23±1.63)ng/mL,差异均有统计学意义(P<0.05)。B组患者临床有效率为95.24%(20/21),A组临床有效率为71.43%(15/21),两组临床有效率比较差异有统计学意义(P<0.05)。A组发生不良反应发生率为23.81%(5/21),B组不良反应发生率为19.05%(4/21),两组患者不良反应发生率比较差异无统计学意义(P>0.05)。有效组患者血药浓度(17.21±6.64)mg/L高于无效组的(10.14±5.48)mg/L;且有效组患者PCT水平(0.65±1.31)ng/mL低于无效组的(2.63±1.87)ng/mL,差异均有统计学意义(P<0.05)。结论:对感染的血液病患者,提高替考拉宁初始负荷剂量可以达到较高的有效血药浓度,临床疗效更好,且不良反应未见增加。对感染的血液病患者进行血药浓度监测,能够一定程度上反映出临床治疗效果,具有临床参考价值。     

Growth hormone and ghrelin secretion in severely obese women before and after bariatric surgery

Objective: The objective was to evaluate ghrelin and growth hormone (GH) interactions and responses to a growth hormone‐releasing hormone (GHRH)/arginine test in severe obesity before and after surgically‐induced weight loss. Research Methods and Procedures: Our study population included 11 severely obese women 39 ± 12 years of age, with a mean BMI of 48.6 ± 2.4 kg/m², re‐studied in a phase of stabilized body weight, with a BMI of 33.4 ± 1.2 kg/m², 18 months after having successfully undergone biliopancreatic diversion (BPD). A GHRH/arginine test was performed before and 18 months after BPD to evaluate ghrelin and GH interactions. Active ghrelin, measured by radioimmunoassay (RIA), and GH, measured by chemiluminescence assay, were assayed before and after the GHRH/arginine test. Results: Fasting serum GH levels and GH area under the curve (AUC) significantly increased from 0.2 ± 0.05 ng/mL to 1 ± 0.3 ng/mL (p < 0.05) and from 514.76 ± 98.7 ng/mL for 120 minutes to 1957.3 ± 665.1 ng/mL for 120 minutes after bariatric surgery (p < 0.05), respectively. Although no significant change in fasting ghrelin levels was observed (573 ± 77.9 before BPD vs. 574.1 ± 32.7 after BPD), ghrelin AUC significantly increased from ?3253.9 ± 2180.9 pg/mL for 120 minutes to 1142.3 ± 916.4 pg/mL for 120 minutes after BPD (p < 0.05). Fasting serum insulin‐like growth factor (IGF)‐1 concentration did not change significantly (133.6 ± 9.9 ng/mL before vs. 153.3 ± 25.2 ng/mL after BPD). Discussion: Our study demonstrates that the mechanisms involved in ghrelin and GH secretion after the secretagogue stimulus (GHRH/arginine) are consistent with patterns observed in other populations.     

Plasma renin and aldosterone levels in obese and non-obese women with polycystic ovary syndrome

ObjetiveTo assess plasma renin and aldosterone levels in obese and non-obese women with polycystic ovary syndrome (PCOS).MethodsObese women (body mass index [BMI] > 30 kg/m2; group A, n = 34) and non-obese women (BMI < 25 kg/m2; group B, n = 13) with PCOS were selected. The control group (group C, n =47) consisted of age-matched women with regular menses and normal ultrasonographic ovaries. Luteinizing hormone, follicle-stimulating hormone, androstenedione, testosterone, sex hormone-binding globulin, serum glucose, insulin, renin, plasma renin activity, and aldosterone levels were measured.ResultsObese and non-obese women with PCOS had higher luteinizing hormone, follicle-stimulating hormone, androstenedione, testosterone, and insulin levels as compared to women in the control group (p < 0.05). Women with PCOS had significantly higher renin levels (group A: 50.2 ± 4.9 picoU/mL, group B: 39.9 ± 2.7 picoU/mL, and group C: 24.6 ± 2.6 picoU/mL), plasma renin activity (group A: 3.7 ± 0.3 ng/mL/h, group B: 3.6 ± 0.3 ng/mL/h, and group C: 2.2 ± 0.4 ng/mL/h), and aldosterone levels (group A: 31.2 ± 3.3 ng/dL, group B: 29.3 ± 2.9 ng/dL, and group C: 22.2 ± 3.9 ng/dL) as compared with controls.ConclusionSignificant differences exist in plasma renin and aldosterone levels between obese and non-obese women as compared with polycystic ovary syndrome and normal controls.     

Circadian Time‐Effect of Orally Administered Loratadine on Plasma Pharmacokinetics in Mice

Little is known about the chronopharmacokinetics of loratadine, a long‐acting tricyclic antihistamine H₁ widely used in the treatment of allergic diseases. Hence, the pharmacokinetics of loratadine and its major metabolite, desloratadine, were investigated after a 20 mg/kg dose of loratadine had been orally administered to comparable groups of mice (n=33), synchronized for three weeks to 12 h light (rest span)/12 h dark (activity span). The drug was administered at three different circadian times (1, 9, and 17 h after light onset [HALO]). Multiple blood samples were collected over 48 h, and plasma concentrations of loratadine and desloratadine were determined by high performance liquid chromatography. There were no significant differences in T_max of loratadine and desloratadine between treatment‐time different groups. However, the elimination half‐life (t1/2) of the parent compound and its metabolite was significantly longer (p<0.01) following administration at 9 HALO (t1/2 loratadine and desloratadine 5.62 and 4.08 h at 9 HALO vs. 4.29 and 2.6 h at 17 HALO vs. 3.26 and 3.27 at 1 HALO). There were relevant (p<0.05) differences in C_max between the three treated groups for loratadine and desloratadine; 133.05±3.55 and 258.07±14.45 ng/mL at 9 HALO vs. 104.5±2.61 and 188.62±7.20 ng/mL at 1 HALO vs. 94.33±20 and 187.75±10.79 ng/mL at 17 HALO. Drug dosing at 17 HALO resulted in highest loratadine and desloratadine total apparent clearance values: 61.46 and 15.97 L/h/kg, respectively, whereas loratadine and desloratadine clearances (CL) were significantly slower (p<0.05) at the other administration times (loratadine and desloratadine CL was 57.3 and 14.22 L/h/kg at 1 HALO vs. 43.79 and 12.89 L/h/kg at 9 HALO, respectively). The area under the concentration‐time curve (AUC) of loratadine and desloratadine was significantly (p<0.05) greater following drug administration at 9 HALO (456.75 and 1550.57 (ng/mL) · h, respectively); it was lowest following treatment at 17 HALO (325.39 and 1252.53 (ng/mL) · h, respectively). These pharmacokinetic data indicate that the administration time of loratadine significantly affected its pharmacokinetics: the elimination of loratadine and its major metabolite desloratadine.     

术后血清PTH下降率预测甲状旁腺全切术后复发的临床价值

目的:探讨甲状旁腺全切术后PTH的监测对于预测手术后是否复发的临床价值,确定具有预测价值的术后PTH的监测时间以及下降率。方法:选取本中心2009年5月至2014年8月收治的338例继发性甲状旁腺机能亢进症(secondary hyperparathyroidism,SHPT)患者作为研究对象,所有患者手术方式均为甲状旁腺全部切除术(total parathyroidectomy,t-PTX)。分别在手术前、术后1小时、术后24小时采集患者的血液标本检测血清PTH水平,并随访至术后一年,观察PTH的下降率与复发的相关性。结果:338名例患者术前、术后1小时和术后24小时的血清PTH水平分别是(1623.2±903.2 pg/m L)、(63.4±80.8 pg/m L)、(20.9±97.0pg/m L)。所有患者术后1小时和术后24小时PTH下降率均大于50%,平均值分别为95.9±5.1%和98.8±4.8%。未复发组术后1小时PTH的下降率中位数为97.1%(63.6-99.9%),复发组术后1小时PTH下降率中位数为79.6%(48.0-96.7%),两组间术后1小时和术后24小时PTH下降率比较差异具有统计学意义(P0.01)。术后1小时及术后24小时PTH下降率的受试者工作特征曲线显示曲线下面积分别为0.907和0.897(P值均0.001)。当PTH下降率为90%时,诊断手术成功的敏感性为87.23%,特异性为88.89%。且术后1小时和术后24小时的PTH下降率基本一致,对于术后复发的临床价值无统计学差异。结论:甲状旁腺全切术后1小时血清PTH的下降率预测术后复发与术后24小时血清PTH的下降率预测手术复发的临床价值相当。     

新型乙酰胆碱酯酶抑制剂Bis(9)-(-)-Meptazinol的小鼠 和大鼠药代动力学研究

目的:研究新型乙酰胆碱酯酶(acetylcholinesterase,AChE)抑制剂Bis(9)-(-)-Meptazinol(B9M)在小鼠和大鼠体内的药代动力学、组织分布和排泄过程。方法:应用本课题组前期报道的大鼠血浆中B9M的LC-MS/MS定量方法:检测B9M皮下和静脉给药后小鼠血浆和脑组织中的含量,计算相应的药代动力学参数,测定B9M小鼠(1.5 mg/kg)和大鼠(1.0 mg/kg)皮下给药后不同时间点的组织分布和粪便、尿液中排泄量。结果:小鼠经皮下注射后,B9M可迅速进入血液(Tmax=0.25 h)血液中消除速度较慢(T_(1/2)=18.09h)绝对生物利用度为115.95%。皮下注射后,B9M在脑内的达峰时间和半衰期分别是8h和18.75h,生物利用度为44.67%。小鼠和大鼠皮下给药后广泛分布于各组织,以脾、肺、肾等血流量大的组织中分布最多。B9M从体内排泄迅速原型药物在小鼠和大鼠尿液和粪便中的排泄量低于3%。结论:皮下给药B9M在小鼠和大鼠体内具有易吸收、分布广泛、易排泄的特点药代动力学特征优良,是极具研发潜力的抗阿尔茨海默病(Alzheimer's disease,AD)新药。