Rectal administration of paracetamol: a comparison of a solution and suppositories in adult volunteers

The pharmacokinetics and tolerability of two dosage forms for rectal administration of paracetamol were compared. A fatty suppository was compared with a solution of 60 mg/ml paracetamol. Both dosage forms were given as 1000 mg doses to 10 healthy adult volunteers. The solution produced peak plasma concentrations significantly faster (t _max) than did the suppository. The peak concentration (C _max) and the area under the curve (AUC₆) were also significantly greater. The pharmacokinetic characteristics of the solution were superior to those of the suppository. No difference in irritation score was identified and no discomfort was reported.     

Direct measurement of probenecid and its glucuronide conjugate by means of high pressure liquid chromatography in plasma and urine of humans

Probenecid with its phase-I metabolites, and phase-II glucuronide conjugate can be analysed by a gradient high pressure liquid chromatographic method. Probenecid glucuronide in plasma with pH 7.4 is not stable and declines to 10% of the original value within 6 h (t_1/21 h). Probenecid glucuronide is stable in urine with pH 5.0, moderately unstable at pH 6.0 (t_1/210 h), and unstable at pH 8.0 (t_1/20.5 h). Probenecid glucuronide is stable in water and 0.01 mol/l phosphoric acid in the autosampler of the high pressure liquid chromatograph. The decrease in concentration in water is 5.5% during 9 h and 0% in diluted acid. Probenecid glucuronide and the phase-I metabolites were not detectable in plasma. The main compound in fresh urine is the phase-II conjugate probenecid glucuronide (62% of a 500 mg dose); the phase-I metabolites are present and only a trace of probenecid is present. The percentage of the dose of the phase-I metabolites varies between 5 and 10, while hardly any probenecid is excreted unchanged (0.33%).     

Plasma concentration profiles after pre-operative rectal administration of a solution of paracetamol in children

An exploratory study in paediatric surgical patients was performed to describe the behaviour of a rectal solution of paracetamol at 20 mg/kg. Four of six patients were able to complete the study. Peak concentration (C_max) and time to peak concentration (t_max) found in the children are comparable to adults studied earlier. After 1.6 hrs (t_max) a peak concentration of 11.7 mg/l (C_max) was reached. The area under the curve (AUC_t=6) and the mean residence time (MRT) were respectively 48.3 mghr/l and 5.2 hrs. The solution appears promising for further study in daily clinical practise.     

托拉塞米胶囊与注射剂在健康人体内的药动学和生物等效性研究

目的 研究托拉塞米胶囊和注射剂在健康人体内的药动学和生物等效性.方法 24名健康受试者随机交叉口服托拉塞米胶囊和注射托拉塞米注射液,剂量均为10 mg.血样经预处理后采用高效液相色谱(HPLC)法测定.结果 试验胶囊、注射液的Cmax分别为(1123±104),(1362±258) μg/L;tmax分别为(1.2±0.3),(1.0±0.3)h;t1/2分别为(4.1±1.0),(4.0±1.0)h;AUC0-t分别为(3583±365),(3844±361)μg/(h·L);AUC0-∞分别为(3838±482)、(3999±463) μg/(h·L);不同剂型之间差异均无统计学意义(P＞0.05).以AUC0-t计算的试验胶囊的相对生物利用度为(97.0±0.5)％.结论 托拉塞米胶囊和注射剂在健康人体内具有生物等效性.     

Direct high pressure liquid chromatographic analysis and preliminary pharmacokinetics of enantiomers of oxazepam and temazepam with their corresponding glucuronide conjugates

Three high pressure liquid chromatographic systems for the separation of oxazepam, temazepam and their glucuronides (system A), the separation of theirR,S glucuronide diastereomers (system B) and the chiral separation of the parent drugs (system C) are described. Preliminary pharmacokinetics ofR,S-oxazepam andR,S-temazepam in a human volunteer reveal that the protein binding of the glucuronides is lower than that of the parent drugs, but that there is no difference in protein binding between theR-oxazepam/temazepam andS-oxazepam/temazepam and their corresponding glucuronides. TheS-glucuronide is the main metabolite formed and excreted by man. The plasma ratioR/S-glucuronide is 11 for both oxazepam and temazepam. The renal clearances ofR-temazepam, andS-temazepam are similar, and those ofR-oxazepam andS-oxazepam tend to be different.     

High pressure liquid chromatographic analysis of the serum concentration of cefuroxime after an intravenous bolus injection of cefuroxime in patients with a coronary artery bypass grafting

A simple reversed-phase high pressure liquid chromatographic method was developed for the determination of cefuroxime in the serum of patients undergoing coronary artery bypass grafting. The serum was cleaned up with a 3.3% solution of perchloric acid in water.Cefalexine was used as an internal standard. Detection was made by a UV multi-wavelength detector. The optimum wavelength for cefuroxime is 275 nm. The absolute recovery of this method was 90.9%; the limit of quantification was 0.7 mg/l. This analytical method was used in a study to investigate the cefuroxime serum concentration-time curves in 26 patients undergoing coronary artery bypass grafting. It was found that one single dose is sufficient to obtain effective serum concentrations.     

法莫替丁肠溶片的血浓度测定及其在人体的药代动力学研究

目的研究法莫替丁的血药浓度测定方法,并应用其进行法莫替丁片剂的人体药代动力学研究。方法采用固相萃取—高效液相色谱(HPLC)紫外检测法测定法莫替丁的血药浓度。18名健康男性志愿者,单剂量口服40mg法莫替丁片剂,不同时间点取静脉血,由血药浓度数据计算各自的主要药代动力学参数。结果所建立的血药浓度测定法能满足药代动力学实验要求。单次服用40mg法莫替丁片剂的主要药代动力学参数血药浓度-时间曲线下面积(AUC)0→12、AUC0→∞、Cmax、Tmax、T1/2分别为(882±185)、(912±187)ng·ml-1·h-1、(171±33)ng/ml、(2.3±0.4)和(2.6±2.7)h。结论法莫替丁的血药浓度测定方法简单、可靠。所得的药代动力学参数与国内外文献报道相似。     

A simple high pressure liquid chromatographic method for the determination of fluorouracil to monitor patients on regional infusion for hepatic metastases

A rapid and sensitive high pressure liquid chromatographic method has been developed for the routine monitoring in serum of the antineoplastic agent fluorouracil, during continuous intraportal administration. Serum spiked with internal standard, bromouracil, was gently shaken for 10 min with ethylacetate at an acidic pH. The evaporated extract was dissolved in the mobile phase containing potassium phosphate buffer. Assays were performed at ambient temperature on a Chrompack LiChrosorb RP 18 column (2×100×3.0 mm) equipped with a guard column. The retention time of fluorouracil was 2–6 min. The calibration curve was linear from 25 to 2,000 ng/ml. The coefficient of variation was 1.6% for within-run precision and 2.9% for day-to-day precision. The mean recovery of fluorouracil was 57%.     

High pressure liquid chromatographic analysis and preliminary pharmacokinetics of sulfaphenazole and its N2-glucuronide and N4-acetyl metabolites in plasma and urine of man

A direct high pressure liquid chromatographic analysis of sulfaphenazole-N2-glucuronide in urine is described. After an oral dose of 439 mg of sulfaphenazole, 0% is excreted unchanged in the urine, < 1% is excreted as N4-acetylsulfaphenazole. As N2-glucuronide 49.4% is excreted in one slow acetylator and 84.8% in one fast acetylator.     

格列齐特片在健康人体内的药代动力学及生物等效性研究

目的研究格列齐特片在健康人体内的相对生物利用度和生物等效性。方法20名健康成年男性志愿者采用随机分组自身交叉对照试验设计,单剂量口服80mg格列齐特片后,用高效液相色谱法测定血浆中药物浓度。结果格列齐特在0.104～12.48μg/ml浓度范围内线性良好(r=0.99988),平均回收率90.125%～104.6%,日内和日间精密度(RSD)均<10.0%。试验制剂和参比制剂的主要药代动力学参数:峰时(Tmax):(4.4±0.9)和(4.0±0.9)h;峰浓度(Cmax):(4.8±0.6)和(5.3±0.8)μg/ml;曲线下面积(AUC)0￣48h:(86±29)和(88±33)mg·L-1·h-1;AUC0￣∞:(99±45)和(103±58)mg·L-·1h-1;消除半衰期(T1/2):(13±4)和(14±5)h。以AUC0￣48h计算的受试制剂的相对生物利用度为(99±9)%。结论建立的分析方法准确灵敏,统计学分析表明两种制剂生物等效。     

HPLC法测定人血浆中伊曲康唑的含量及其药代动力学研究

目的建立HPLC法测定人血浆中伊曲康唑含量方法及药代动力学特征的研究。方法选取20名健康受试者高脂饮食后随机交叉口服受试制剂和参比制剂伊曲康唑片100mg。采用HPLC-UV法测定伊曲康唑的血药浓度。结果受试制剂的相对生物利用度为(99.7±9.2)%。结论伊曲康唑的药代动力学特征较明显,表明两制剂具有生物等效性。     

美洛昔康分散片在健康人体内的药代动力学和生物等效性研究

目的研究美洛昔康分散片在24名健康志愿者体内的药代动力学和生物等效性。方法采用两制剂双周期交叉试验设计,单剂量口服15mg的美洛昔康受试制剂或参比制剂,用高效液相色谱法测定血浆中美洛昔康药物浓度。结果美洛昔康在0.015～3μg/ml范围内线性良好(r=0.9996),平均回收率89.43%～103.17%,日内和日间精密度(RSD)均<6.00%。试验制剂和参比制剂的t1/2分别为(22±7)和(22±7)h,Cmax分别为(1.32±0.27)和(1.42±0.32)μg/ml,Tmax分别为(4.6±1.1)和(4.8±1.9)h;AUC0～96分别为(42±14)和(45±14)mg·L-1·h-1;AUC0～∞分别为(45±17)和(48±18)mg·L-1·h-1。受试制剂对参比制剂的相对生物利用度为(93±10)%。两者的lnAUC、lnCmax经方差分析和双单侧检验证明差异无统计学意义(P>0.05),两制剂的Tmax经非参数法检验差异无统计学意义(P>0.05)。结论美洛昔康分散片和参比制剂具有生物等效性。     

反相高效液相色谱法测定大鼠血浆中补阳还五汤总生物碱中川芎嗪的含量及药代动力学研究

目的对大鼠血浆中补阳还五汤及总生物碱中川芎嗪的含量进行了测定,并对其药代动力学研究。方法采用反相高效液相色谱(RP-HPLC)法测定,其条件为色谱柱:C18柱,4.6mm×250mm,5μm;检测波长:278nm;流动相:甲醇∶水(33∶67);流速:1ml/min;柱压:(20.7±0.4)MPa;温度:35℃。药代动力学参数采用3P87软件处理。结果血浆样品中川芎嗪线性范围为51.4￣308.4ng,r=0.9997,回收率为98.85%,sx为1.492%。川芎嗪药代动力学参数:复方:t1/2α为27.73min,t1/2β为8197min;k12为0.02067min-1,k21为0.003860min-1,k10为0.0005470min-1;总生物碱:t1/2α为27.72min,t1/2β为9043min;k12为0.02135min-1,k21为0.003117min-1,k10为0.0006120min-1。结论该法快速、简便,准确。补阳还五汤复方及总生物碱中川芎嗪药代动力学为二室模型。中药复方成分组合对药代动力学参数有一定影响。     

帕罗西汀片在健康人体的药动学与生物等效性

［摘要］目的研究帕罗西汀片剂在健康人体的药动学过程，并比较两种帕罗西汀片剂的生物等效性。方法男性健康志愿者20例，随机交叉单剂量口服帕罗西汀片试验制剂和参比制剂40 mg后，用高效液相色谱法测定血浆帕罗西汀浓度。并用3P97药动学软件进行参数计算及评价两种制剂的生物利用度和生物等效性。结果单剂量口服试验制剂和参比制剂后血浆帕罗西汀的主要药动学参数如下：Cmax分别为（62.78±17.34）和（64.74±18.43） ng·mL 1；tmax 分别为（5.13±1.37） 和（5.64±1.84） h；t1/2分别为（19.85±5.72） 和（20.03±5.33） h；AUC0 120分别为（1 043.21±297.33）和（1 076.47±309.49） ng·h·mL 1；AUC0－inf分别为（1 358.35±443.73）和（1 386.75±476.54） ng·h·mL 1。试验制剂与参比制剂的人体相对生物利用度为F0 120（98.9±16.3）%,F0 inf（96.3±18.2）%。结论两种帕罗西汀片剂具有生物等效性。     

Pharmacokinetics of epidurally administered nicomorphine with its metabolites and glucuronide conjugates in patients undergoing pulmonary surgery during combined epidural local anaesthetic block and general anaesthesia

After epidural administration of 15 mg 3, 6-dinicotinoylmorphine (nicomorphine) in 10 patients undergoing pulmonary surgery, the parent compound was quickly metabolized into the metabolites 6-mononicotinoylmorphine and morphine. The mean apparent half-lives (±SD) of elimination were 10 min (0.165 h ± 0.053 h) for 3, 6-dinicotinoylmorphine and 1.77 h ± 1.23 h for 6-mononicotinoylmorphine. Morphine is subsequently metabolized into morphine-3-glucuronide, and morphine-6-glucuronide. The apparent half-lives of morphine, morphine-3-glucuronide, and morphine-6-glucuronide are similar: 3.63 h ± 1.63 h, 4.10 h ± 0.57 h, and 4.20 h ± 1.64 h respectively. The possible glucuronide conjugate of 6-mononicotinoylmorphine was not detected. The prodrug 3, 6-dinicotinoylmorphine was biotransformed into three active compounds: 6-mononicotinoylmorphine, morphine, and morphine-6-glucuronide.     

异钩藤碱药动学及其含量测定方法研究概述△

目的:归纳异钩藤碱药动学及其含量测定方法的研究进展。方法:查阅国内外有关文献进行综合分析。结果:异钩藤碱是中药钩藤中的主要生物碱之一,目前主要采用HPLC、反相HPLC等方法检测动物组织和血液中异钩藤碱浓度,并进行了异钩藤碱在大鼠、兔、猫体内的药动学研究;采用HPLC、超高效液相色谱、非水毛细管电泳、高效毛细管电泳、薄层色谱傅里叶变换表面增强拉曼散射法测定钩藤药材中异钩藤碱的含量。结论:虽然对异钩藤碱药动学及其含量检测方法研究取得了一定成果,随着科技发展和高端检测仪器的应用,还需采用更加快速、便捷、精确的检测方法,为异钩藤碱今后的进一步研究和开发提供技术支撑。     

Pharmacokinetics, N1-glucuronidation and N4-acetylation of sulfadimethoxine in man

Sulfadimethoxine is metabolized byO-dealkylation, N4-acetylation and N1-glucuronidation. In man, only N1-glucuronidation and N4-acetylation takes place, leading to the final double conjugate N4-acetylsulfadimethoxine-N1-glucuronide. The N1-glucuronides are directly measured by high pressure liquid chromatography. When N4-acetylsulfadimethoxine is administered as parent drug, 30% of the dose is N1-glucuronidated and excreted. Fast acetylators show a shorter half-life for sulfadimethoxine than slow acetylators (27.8±4.2 h versus 36.3±5.4 h; P=0.013), similarly the half-life of the N4-acetyl conjugate is also shorter in fast acetylators (41.3±5.2 h versus 53.5±8.5 h, P=0.036). No measurable plasma concentrations of the N1-glucuronides from sulfadimethoxine are found in plasma. N1-glucuronidation results in a 75% decrease in protein binding of sulfadimethoxine. N4-acetylsulfadimethoxine and its N1-glucuronide showed the same high protein binding of 99%. Approximately 50–60% of the oral dose of sulfadimethoxine is excreted in the urine, leaving 40–50% for excretion into bile and faeces.     

Pharmacokinetics of oxycodone hydrochloride and three of its metabolites after intravenous administration in Chinese patients with pain

ObjectivesThe aim of this study is to evaluate the pharmacokinetic profile of oxycodone and three of its metabolites, noroxycodone, oxymorphone and noroxymorphone after intravenous administration in Chinese patients with pain.MethodsForty-two subjects were assigned to receive intravenous administration of oxycodone hydrochloride of 2.5, 5 or 10 mg. Plasma and urine samples were collected for up to 24 h after intravenous administration of oxycodone hydrochloride.ResultsPharmacokinetic parameters showed that mean values of C_max, AUC_0–t and AUC_0–∞ of oxycodone were dose dependent, whereas T_max and t_1/2 were not. The mean AUC_0–t ratio of noroxycodone to oxycodone ranged from 0.35 to 0.42 over three doses, and those of noroxymorphone, or oxymorphone, to oxycodone were ranging of 0.06–0.08 and 0.007–0.008, respectively. Oxycodone and its three metabolites were excreted from urine. Approximately 10% of unchanged oxycodone was recovered in 24 h. Most adverse events (AEs) reported were mild to moderate. The frequently occurred AEs were dizziness, nausea, vomiting, drowsiness and fatigue. No dose-related AEs were found.ConclusionOur pharmacokinetics of oxycodone injection in Chinese patients with pain strongly support continued development of oxycodone as an effective analgesic drug in China.     

脑梗死患者血清磷酸二酯酶活性的变化及意义

目的研究脑梗死患者外周血磷酸二酯酶(PDE)活性的变化及意义。方法应用高效液相色谱法(HPLC)检测298例脑梗死患者和181例对照组外周血白细胞的PDE活性,同时检测他们的血生化指标,收集临床资料,进行统计分析。结果脑梗死组外周血PDE活性为(13.78±3.12),对照组为(7.36±2.34),差异有统计学意义(P<0.01),但外周血PDE活性与病情的严重程度无关。Logistic回归分析表明,外周血PDE活性水平与脑梗死有关(P<0.01)。结论脑梗死患者PDE活性增高,HPLC能简单易行、精密可靠地测定外周血白细胞的PDE活性,PDE在脑梗死的发病中可能起重要作用。     

人血浆中环丙沙星的高效液相色谱测定及其药物动力学研究

建立了测定血浆中环丙沙星浓度的反相离子对高效液相色谱法，色谱柱采用Ｃ１８Ｓｐｈｅｒｉｓｏｒｂ柱（２５ｃｍ×４．６ｍｍ，５μｍ），流动相为甲醇（０．００８ｍｏｌ／Ｌ）磷酸盐缓冲液（０．５ｍｏｌ／Ｌ）四丁基溴化铵（３０∶７５∶４，ｖ／ｖ／ｖ，ｐＨ２．６）。检测波长为２７６ｎｍ。方法检测限为４０ｎｇ／ｍｌ（Ｓ／Ｎ≥２）。该法简单，用乙腈沉淀蛋白后直接进样。应用该法研究了８名志愿者单剂量随机交叉服用环丙沙星片剂及干糖浆两种剂型后的药物动力学，结果显示，两种剂型的药物动力学参数无显著性差异，干糖浆的相对生物利用度为片剂的８４％。