健康志愿者口服大黄制剂后大黄酸在人体内的药代学研究

目的:研究健康志愿者口服大黄制剂后大黄酸在人体内的药代学过程。方法:12名健康自愿者单次口服大黄制剂(50mg.kg^-1),分别在服药0,0.083,0.5,1,1.5,2,3,4,5,7,10h后11个不同时间点取静脉血,血药浓度采用高效液相色谱法(HPLC)测定,药代学参数采用3P97程序计算。结果:人口服大黄制剂后,大黄酸以很快的速度从肠道被吸收入血。其主要药代学参数为最大血药浓度(C_max)(3.20±1.08)μg.mL^-1;最大浓度时间(t_max)(1.03±0.41)h;分布半衰期(t_1/2α)(0.21±0.02)h;消除半衰期(t_1/2β)(2.68±1.09)h;平均滞留时间(MRT)(5.31±1.78)h;药时曲线下面积(AUC_0-∞)(1573.08±366.48)μg.mL^-1.min^-1。结论:大黄制剂口服后大黄酸能迅速被人体吸收,其药代学符合二室模型。     

Pharmacokinetic analysis of rhein in Rheum undulatum L

This research aims to identify the main active compounds of Rhei undulati Rhizoma (roots of Rheum undulatum LINNE) and determine the types of anthraquinones absorbed into the body and their pharmacokinetic parameters. The boiling-water extract of the herb was administered to 12 healthy volunteers (9 men/3 women) at a dosage of 100 mg/kg the anthraquinone levels in plasma were determined with TLC, HPLC, and LC-MS. Rhein was the only anthraquinone compound absorbed by the body as determined for plasma analysis of the volunteers. The elimination rate constant of rhein in Rhei undulati Rhizoma was 0.23+/-0.02/h and the half life was 3.38+/-0.35 h. This experiment confirmed that rhein is the most important active compound absorbed by the body among anthraquinones contained in Rhei undulati Rhizoma, indicating that rhein is a promising marker substance to evaluate Rhei Rhizoma and Rhei undulati Rhizoma.     

Effect of piperine on the steady-state pharmacokinetics of phenytoin in patients with epilepsy

Piperine, the active principle of Piper longum, Piper nigrum and Zingiber officinalis, has been reported to enhance the oral bioavailability of phenytoin in human volunteers. The objective of this study was to explore the effect of a single dose of piperine in patients with uncontrolled epilepsy on the steady-state pharmacokinetics of phenytoin. Two groups of 10 patients each receiving either a 150 mg or 200 mg twice daily dose of phenytoin were selected. Twelve hours after the night dose, venous blood samples were collected at 0, 0.5, 1, 2, 4, 6, 9, 12 h after administration of phenytoin. On the next study day, piperine 20 mg was administered along with phenytoin and samples were collected similarly. The mean plasma drug concentrations at different time points and the pharmacokinetic parameters before and after piperine administration were compared by Student's t-test. Piperine increased significantly the mean plasma concentration of phenytoin at most of the time points in both dose groups. There was a significant increase in AUC((0-12h)) (p < 0.01), C(max) (p < 0.001) and K(a) (p < 0.05) whereas the changes in K(el) and t(max) were not significant. The results showed that piperine enhanced the bioavailability of phenytoin significantly, possibly by increasing the absorption.     

大黄用于抗氧化的日服用次数研究

目的采用大黄含药血清体外抗氧化效应动力学结合大黄蒽醌类成分的整合药代动力学的方法研究大黄的日服用次数。方法将24只大鼠随机分为3组,每组8只,每天分别灌服大黄提取物3.6g/kg,1次/天、1.8g/kg,2次/天和1.2g/kg,3次/天,分别于第一次给药前(0小时)及给药后5、10、15、30分钟,1、2、4、6、8、10、12、24小时眼眶后静脉取血,用于测定大鼠血中大黄酸、芦荟大黄素、大黄素、大黄酚以及大黄素甲醚五种蒽醌类成分的含量和对超氧阴离子的抑制率。计算上述成分在大鼠体内的药动学参数,利用各成分曲线下面积(AUC0-∞)百分率作为自定义权重系数,得到其整合药代动力学曲线,再与抗氧化效应动力学进行相关性分析,以此来制定大黄用于抗氧化时合理的日服用次数。结果大黄蒽醌类成分整合药代动力学与含药血清体外抗氧化效应动力学具有良好的相关性。每日给药2次组整合药代动力学AUC及抗氧化效应动力学AUC均明显高于每日给药1次和3次组。结论大黄用于抗氧化时以每日服用两次为宜。     

匹卡米隆片在健康人体的药动学研究

 目的 探讨匹卡米隆片在健康人体的药动学。 方法 采用液 - 质联用法测定 12 名健康志愿者口服匹卡米隆片后的血药浓度 , 计算药动学参数。 结果 受试者单次口服匹卡米隆片 50 ， 100 和 200 mg 后的实测平均达峰时间 <> t _max 分别为 (0.73 ± 0.41) ， (0.67 ± 0.33) 和 (0.67 ± 0.31)h ； <> t _1/2 分别为 (0.68 ± 0.22) ， (0.89 ± 0.41) 和 (0.91 ± 0.21)h ；平均 <> ρ _max 分别为 (1 328.75 ± 552.33) ， (2 460.83 ± 571.19) 和 (4 415.00 ± 1 077.45)μg·L^{- 1} ； AUC _{0 -t<>n} 平均值分别为 (1 617.37 ± 575.48) ， (3 117.08 ± 620.93) 和 (5 987.01 ± 1 365.57)μg·h·L^{- 1} ； AUC _{0 - ￥} 平均值分别为 (1 697.45 ± 584.78) ， (3 227.39 ± 641.54) 和 (6 192.36 ± 1 388.59)μg·h·L^{- 1} 。 结论 血浆药物的 <> ρ _max 和 AUC 随剂量的增大而增加，匹卡米隆的体内药代过程无性别差异。     

西罗莫司胶囊在人体内的生物等效性评价

 目的 评价国产西罗莫司胶囊与市售西罗莫司口服液在中国健康男性体内的生物等效性。方法 入选22名男性健康志愿者,随机交叉单剂量po西罗莫司胶囊或西罗莫司口服液5 mg,液质联用法测定全血中西罗莫司浓度。结果 西罗莫司胶囊及口服液的药动学参数分别如下：ρ_max分别为(26.62±9.97)和(25.28±5.98) ng·mL^-1;t_max分别为(2.27±0.55)和(1.91±2.33) h;t_1/2分别为(73.07±13.81)和(65.49±17.00) h;AUC_0-t分别为(372.3±146.2)和(368.2±275.0) ng·h·mL^-1,AUC_0-∞分别为(466.8±194.3)和(442.3±324.4) ng·h·mL^-1。相对生物利用度F_0-t (112.4±34.61)%,F_0-∞(117.2±39.93)%。经双单侧t检验确认,2种制剂的ρ_max、AUC_0-t及AUC_0-∞均等效,非参数检验表明,试验药西罗莫司胶囊的t_max比参比口服溶液大,有显著性差异（P<0.05）。结论 除t_max外,国产西罗莫司胶囊与市售西罗莫司口服液的ρ_max和AUC_0-t生物等效。
     

注射用头孢替坦二钠在中国健康人体内的药动学

 目的 研究中国健康受试者静脉注射头孢替坦二钠后的药动学特征。方法 30名健康受试者随机分为3组,男、女各半,分别静脉滴注头孢替坦二钠0.5、1.0、2.0 g,进行低、中、高单剂量药动学研究。1.0 g剂量组并进行多剂量药动学研究。采用HPLC-UV测定血浆中头孢替坦二钠的浓度。应用DAS2.1.1软件计算药动学参数,并进行统计分析。结果 30名健康受试者分别单次静脉滴注头孢替坦二钠0.5,1.0,2.0 g的主要药动学参数如下：ρ_max为(68.03±15.95)、(110.77±17.67)、(225.34±19.63) mg·L^-1;AUC_0-15为(242.88±56.60)、(415.22±54.24)、(856.18±82.72) mg·h·L^-1;t_1/2为(3.67±0.48)、(3.69±0.40)、(3.53±0.26) h。多次给药的主要药动学参数如下：ρ_max为(123.60±15.74) mg·L^-1 ;AUC_0-15为(444.38±62.78) mg·h·L^-1;AUC_SS为(426.87±59.36) mg·h·L^-1;t_1/2为(3.29±0.36) h;ρ_av为(35.57±4.95) mg·L^-1。结论 注射用头孢替坦二钠单剂量静脉滴注后在0.5～2.0 g内呈线性动力学特征;连续给药后在体内无蓄积;性别对注射用头孢替坦二钠的体内药动学无差异。     

Pharmacokinetics of anthraquinones in Xiexin decoction and in different combinations of its constituent herbs

Xiexin decoction (XXD), a classic pyretolysis formula, is composed of Rhei Rhizoma (DH), Radix Scutellaria (HQ) and Coptis Chinensis (HL) and is commonly used in the clinical setting. The aim of this study was to investigate the pharmacokinetic differences of the five anthraquinones in rats after oral administration of XXD and different combinations of its constituent herbs. Twenty rats were randomly divided into four groups and were administered one of the four extracts: DH, DH-HQ, DH-HL and XXD (DH-HQ-HL) via intragastric gavage. Anthraquinone concentrations in plasma were determined by an HPLC technique. Pharmacokinetic parameters were calculated from the plasma concentration-time data. Compared with DH alone, the DH-HL combination decreased C(max) of all five anthraquinones and AUC of four anthraquinones (except physcion), and the DH-HQ combination decreased AUC of aloe-emodin and C(max) of rhein. Finally, XXD increased AUC of all five anthraquinones compared with DH-HL combination. These results showed that the oral bioavailabilities of five anthraquinones were decreased significantly by combining DH with HL, whereas HQ weakened the effect of HL that inhibited the absorption of anthraquinones.     

大黄复方保留灌肠辅助治疗慢性肾脏病疗效及对患者生活质量的影响

目的:研究大黄复方保留灌肠辅助治疗慢性肾脏病的治疗效果及对患者生活质量的影响。方法:纳入CKD患者170例,随机分为对照组和观察组,各85例。对照组患者进行常规对症治疗,观察组在对照组的基础上进行大黄复方保留灌肠。比较两组的治疗效果,治疗前后的GSRS评分以及生活质量评分。结果:两组的治疗有效率比较,差异无统计学意义(P>0.05)。对照组CKD分期进展率明显高于观察组(P<0.05)。治疗后,观察组反酸、腹胀、大便干结、恶心呕吐和嗳气评分均明显低于对照组(P<0.05),症状影响、躯体功能、情感生活、社会功能、社会角色、精力、肾病影响、疼痛、社会情感评分均明显高于对照组(P<0.05)。结论:大黄复方保留灌肠应用于CKD的辅助治疗中,疗效确切,有助于减缓疾病进展,减轻患者消化道症状,提高患者的生活质量。     

多剂量氟罗沙星在健康人体内的药代动力学研究

 对１０例健康志愿者单次及多次ｐｏ４００ｍｇ氟罗沙星后进行药代动力学研究，血药浓度及尿药浓度均采用微生物法和ＨＰＬＣ测定。单次及多次给药后的数据分别采用３Ｐ８７及ＳＳＤ程序处理，药－时曲线符合二室模型。单次ｐｏ４００ｍｇ氟罗沙星后，其微生物法和ＨＰＬＣ测定结果分别为Ｔ＿（ｍａｘ）２．２０ｈ和２．１３ｈ，ｃ＿（ｍａｘ）５．４９μｇ／ｍｌ和５．５５μｇ／ｍｌ，Ｔ＿（１／２β）１０．１４ｈ和１０．５５ｈ。０～４８ｈ尿药回收率分别为：５６．６７％和５２．２５％。经ｔ检验２种方法的测定结果无显著性差异（Ｐ＞０．０５）。在每日４００ｍｇ连续８ｄ的多次ｐｏ给药实验中，第１ｄ和第８ｄ的药代动力学参数经ｔ检验无显著性差异（Ｐ＞０．０５），说明本品每天１次的重复给药无明显蓄积现象。     

大黄不同剂量保留灌肠治疗早期尿毒症疗效观察

[目的]观察不同剂量大黄制剂保留灌肠治疗早期尿毒症的临床疗效。[方法]将符合入选标准的60例早期尿毒症患者随机分为低剂量组(30例)和高剂量组(30例),分别给予10g和25g生大黄制剂保留灌肠,12天为1个疗程。观察症状和体征以及血肌酐的变化情况。[结果]高剂量组疗效优于低剂量组(P<0.05)。[结论]25g生大黄制剂保留灌肠治疗早期尿毒症患者的临床疗效优于较低剂量组。     

HPLC-MS法测定血浆中的帕罗西汀及人体内药动学研究临床药学

 目的研究盐酸帕罗西汀的血浆浓度测定方法及其在人体内的药动学。方法18名健康男性志愿者，单剂量口服盐酸帕罗西汀片，在设计的时间点取静脉血，血药浓度采用液相色谱 质谱(HPLC MS)法测定。药动学参数采用3P97程序计算。结果单次服用40 mg盐酸帕罗西汀片后的主要药动学参数Ka，AUC_0～96，AUC_0～∞，c_max，t_max，CL分别为(0.89±0.28) h^-1，(576.2±236.0) ng·h·mL^-1，(596.8±234.5) ng·h·mL^-1，(26.3±9.6) ng·mL^-1，(3.89±2.1) h，(0.09±0.05) L·h^-1。结论盐酸帕罗西汀片在中国人体内口服吸收缓慢，约4 h达到血药浓度峰值，平均消除半衰期为19～23 h与国外文献报道相似。     

头孢拉定对黄芩苷大鼠体内药动学的影响

目的研究头孢拉定对黄芩苷在大鼠体内药动学的影响。方法用HPLC-ECD方法测定头孢拉定和黄芩苷合并给药组与黄芩苷单独给药组黄芩苷在大鼠体内的血药浓度,比较两者的药动学参数。结果头孢拉定和黄芩苷合并给药组黄芩苷Cmax为(782.63±469.37)ng/mL,AUC0~24h为(8407.86±3476.14)ng/mL·h;黄芩苷单独给药组黄芩苷Cmax为(2645.62±601.42)ng/mL,AUC0~24h为(28952.90±5731.42)ng/mL·h。结论两者药动学参数存在显著性差异(P<0.05),口服头孢拉定严重降低了黄芩苷的血药浓度。提示临床应合理用药。     

小承气汤中大黄酸在大鼠体内的药动学研究

目的 研究小承气汤中大黄与厚朴、枳实配伍对大黄酸在大鼠体内药动学过程的影响.方法 大鼠分别给予大黄及小承气汤,高效液相色谱法测定大黄酸在大鼠体内血药浓度变化.色谱柱为Diomansil C18(4.6 mm×150 mm,5μm),流动相为甲醇-水-冰醋酸(77∶22∶1);检测波长为428 nm;流速为1.0 mL/min.血药浓度数据采用3P97药动学软件进行分析.结果大黄酸血药浓度在1.0～15 μg/mL范围内线性关系良好.大鼠给予大黄及小承气汤后,大黄酸血药浓度-时间曲线均符合二房室模型,其主要药动学参数AUC、Cmax和CL均存在显著性差异(P＜0.05).结论 大黄与厚朴、枳实配伍后,使大黄酸在大鼠体内的血药浓度降低.     

复方赖诺普利片人体药动学研究

目的:探讨复方赖诺普利片在健康受试者体内的药动学性质。方法:采用液质联用测定12名健康志愿者在单剂量和多剂量口服复方赖诺普利片后的人体药动学参数。结果:该法所测得峰形良好,无杂质峰干扰测定,基线平稳;另外,将多剂量与单剂量的药动学参数进行比较发现,两组的药动学参数基本一致。结论:复方赖诺普利片主要药动学参数单剂量和多剂量给药差异无显著性,赖诺普利和氢氯噻嗪在人体内不存在"蓄积现象"。     

大黄酸聚乳酸纳米粒的制备及大鼠体内药动学研究

 目的 制备大黄酸聚乳酸纳米粒,并考察其在大鼠体内的药动学特征,以期提高大黄酸口服生物利用度。方法 以聚乳酸为载体材料,采用改良的自乳化溶剂扩散法制备大黄酸聚乳酸纳米粒;透射电镜观察纳米粒的形态;激光粒度仪考察粒径和Zeta电位;超速离心法测定其包封率及载药量;透析袋法研究其体外释药特性;以大黄酸混悬液为对照组,进行大鼠口服大黄酸聚乳酸纳米粒的药动学研究。结果 纳米粒外观呈圆形或类圆形,平均粒径为（134.37±3.61）nm,Zeta电位为（-18.41±0.07） mV,包封率和载药量分别为（60.37±1.52）%和（1.32±0.09）%;体外释药符合Higuchi方程;大鼠口服大黄酸混悬液和纳米粒后,ρ_max分别为（5.788±0.15）和（11.607±0.56）mg·L^-1,t_max分别为（0.193±0.01）和（1.102±0.13）h, AUC_0→t分别为（8.077±2.98）和（34.583±3.93）mg·h·L^-1,t_1/2β分别为（3.319±0.23）和（21.721±6.13）h。结论 聚乳酸纳米粒可显著改善大黄酸的药动学行为,有效提高其口服生物利用度。
     

不同给药途径治疗湿热瘀阻型复发性盆腔炎疗效比较

目的:比较中药保留灌肠与中药熏蒸2种给药途径治疗湿热瘀阻型复发性盆腔炎的临床疗效。方法:将60例复发性盆腔炎患者随机分为灌肠组、熏蒸组各30例。灌肠组予中药口服配合中药保留灌肠治疗;熏蒸组予中药口服配合中药熏蒸治疗,2组均以20天为1个疗程,连续治疗2个疗程后比较临床疗效。结果:总有效率灌肠组为96.67%,熏蒸组为76.67%,2组比较差异有统计学意义(P0.05)。复发率灌肠组为10.00%,熏蒸组为26.67%,2组比较差异有统计学意义(P0.05)。结论:中药灌肠治疗湿热瘀阻型复发性盆腔炎的临床疗效优于中药熏蒸给药治疗。     

Assessment of the renal protection and hepatotoxicity of rhubarb extract in rats

Aim of the study

Rhubarb is well used to treat chronic renal failure (CRF) in China and Japan, but recent studies reported that the anthraquinone derivatives contained in rhubarb had nephrotoxicity. In this investigation an attempt was made to assess the value and toxic potential of rhubarb to treat CRF.

Materials and methods

Histopathologic and biochemical tests combined with toxicokinetic analysis were performed to investigate the nephrotoxic potential and protective effect of rhubarb extract.

Results

In normal rat groups, no death was observed and no renal lesion was found after repetitive administration of rhubarb for 3 weeks. The survival rate, pathologic conditions and biochemical indexes of CRF rats treated with rhubarb at two dosages were all improved and significant amelioration was found in the low dosage group compared to the untreated CRF group. Rhein was the mainly absorbable anthraquinone derivative into systemic circulation after oral administration and the area under curve of rhein in CRF groups was lower than that in normal groups at same dosage.

Conclusions

After 3 weeks of administration of rhubarb extract, there was evidence of protective effect to CRF rats, while incidences of hepatotoxicity with minimal to mild hyaline droplets were also observed in normal rats.     

日服用次数对大黄体外抗氧化效应的影响

目的:研究日服用次数对大黄含药血清体外抗氧化效应的影响,制定大黄用于抗氧化的合理日服用次数.方法:Wistar大鼠日服1次组(G1),2次组(G2),3次组(G3),分别每日灌服大黄提取物3.6 g·kg-11次、1.8 g·kg-12次、1.2g·kg-13次,分别于第1次给药前(0 h)及给药后0.083,0.167,0.25,0.5,1,2,4,6,8,10,12,24 h眼眶后静脉取血,用于测定大黄含药血清体外对超氧阴离子自由基(O2+)、二苯代苦味酰基自由基(DPPH)以及羟基自由基的清除抗氧化实验,并对其进行房室模型的拟合和参数计算,得到抗氧化效应-时间曲线(E-T曲线),制定大黄用于抗氧化时合理的日服用次数.结果:日服用次数与大黄抗氧化作用的强弱显著相关,给药2次E-T曲线下面积(AUCE)明显高于给药1次和3次(P＜0.05).结论:大黄用于抗氧化日服用次数以每日2次为宜.