复方氨酚曲马多片中对乙酰氨基酚的人体药代动力学研究

目的研究氨酚曲马多片在中国健康人体内的药代动力学特性。方法10名健康志愿者（男女各半）单剂量口服2片氨酚曲马多片（每片曲马多／对乙酰氨基酚为37．5mg／325mg）。对乙酰氨基酚血药及尿药浓度采用高效液相色谱．紫外（HPLC．UV）检测法测定。结果受试者单次口服给药后,以HPLC-UV法测血浆及尿液中对乙酰氨基酚浓度。采用DAS软件计算对乙酰氨基酚的药代参数。Cmax为（10．95±7．85）mg·L^-1,‰为（0．83±0．29）h,t1／2为（2．09±0．34）h,AUC0-24为（26．93-I-11．64）mg·h·L^-1,AUC0-∞为（27．74±11．57）mg·h·L^-1,尿液中24h以原形排泄百分比（2．90±1．32）％;受试者各项检查未见异常,无不良反应发生。结论对血浆药代动力学参数及尿中药物排泄量进行性别单因素方差分析,结果未显示性别差异。该药在试验剂量下具有良好的安全性。     

对乙酰氨基酚凝胶在人体的药动学和生物利用度

８名健康男性志愿者交叉服用５００ｍｇ剂量的对乙酰氨基酚凝胶剂和片剂。血药浓度采用ＨＰＬＣ测定。对乙酰氨基酚凝胶剂的药动学参数：Ｔ１／２（Ｋａ）０．３０±０．２２ｈ，Ｔ１／２（Ｋｅ）２．１±０．４ｈ，Ｔｍａｘ１．０±０．４ｈ，Ｃｍａｘ５．１±１．５μｇ／ｍｌ，ＡＵＣ２１±５（μｇ／ｍｌ）·ｈ。这些参数与片剂的相似，凝胶剂相当于片剂的生物利用度为１０５．１％     

Comparison of the pharmacokinetics of paracetamol from two generic products in patients after total gastric resection

Gastrectomy leads to pathophysiological changes within the alimentary tract, which may affect drug absorption and pharmacokinetic parameters (PK). The need to apply orally administered analgesics in this group of patients is often related with alternative application of currently available generic products. Thus, from the clinical point of view it is necessary to evaluate the PK of these drugs to confirm their equivalence. The aim of the study was therefore an analysis of the pharmacokinetics of paracetamol from two generic products in patients after total gastric resection. The research was carried out on two groups of patients after gastrectomy with Roux-en-Y reconstruction (n = 30; mean [SD] age, 63.0 [11.5] years; weight, 67.6 [13.7] kg; and height, 166.4 [9.1] cm). The patients received paracetamol in a single orally administered dose of 1,000 mg. Blood samples were collected within 6 h of drug administration. The concentration of paracetamol and paracetamol glucuronide in the blood plasma was marked by means of a validated high-pressure liquid chromatography with ultraviolet detection (HPLC-UV). The main PK for paracetamol in group 1 (n = 17) and 2 (n = 13) were as follows: C(max), 9.46 (3.66) and 12.79 (5.32) μg/ml, respectively (p = 0.0517); AUMC(0-t), 77.64 (30.37) and 51.01 (15.76) μg h(2)/ml (p = 0.0046); AUC(0-inf), 41.61 (23.52) and 30.28 (9.74) μg h/ml (p = 0.0862); t(max), 1.68 (0.63) and 0.50 (0.25) h (p < 0001). The obtained C(max) and AUC values in patients after gastrectomy were reduced in comparison with healthy subjects. Total gastrectomy therefore affected the pharmacokinetics of paracetamol administered in tablets. In our patients, we also observed significant differences between the PK of paracetamol and two generic preparations. These two drugs can thus be used interchangeably, but with caution.     

Investigating paracetamol pharmacokinetics using venous and capillary blood and saliva sampling

Objective The aim of this study was to develop, validate and apply a high performance liquid chromatography (HPLC) assay for analysis of paracetamol, paracetamol glucuronide and paracetamol sulfate in plasma (venous and capillary) and saliva to study paracetamol pharmacokinetics in healthy volunteers. Methods Samples were prepared using protein precipitation and analysed using reverse phase HPLC with UV detection. This assay was applied to venous and capillary plasma and saliva samples from 20 healthy volunteers after paracetamol 1 g four times daily for three days. Key findings The HPLC assay for paracetamol and its metabolites was found to be sensitive and selective in plasma and saliva samples over the range 0.05–50 mg/l with an inter‐ and intraday precision and accuracy within 11.2% and 11.1%, respectively. Mean recoveries for all analytes were > 88%. A study of paracetamol pharmacokinetics in healthy volunteers found close agreement between the sampling matrices for paracetamol and metabolites (metabolites were not detected in saliva). The value for area under the concentration–time curve over the 6 h dosing interval of venous plasma (45.3 ± 12.9 mg/l.h) was significantly higher than that observed for capillary plasma (33.8 ± 12.9 mg/l.h) or saliva (35.1 ± 9.4 mg/l.h; P > 0.01). Conclusions Capillary blood and saliva collection were found to be reliable sampling matrices for the evaluation of paracetamol pharmacokinetics, although paracetamol metabolites were not detected in saliva.     

HPLC法测定复方氨酚烷胺片中对乙酰氨基酚的含量

目的探讨复方氨酚烷氨片中的对乙酰氨基酚的含量的测定方法.方法采用C18柱以水-甲醇(65:35)为流动相,流速为1 ml·min-1,检测波长为249 nm.结果对乙酰氨基酚在40～200 mg·L-1线性良好(r=0.999 9)平均回收率为100.1%,RSD=0.50%.结论该方法简便快速,结果准确.     

感冒灵颗粒中药成分对化药成分人体药动学的影响研究

目的研究感冒灵颗粒中中药成分对对乙酰氨基酚、咖啡因和氯苯那敏人体药动学的影响。方法 12名健康男性志愿者,按2×2交叉试验设计,分别单次、多次口服感冒灵颗粒(试验制剂)或相应的化药组合(参比制剂),血浆中对乙酰氨基酚浓度采用HPLC-UV法测定,咖啡因和氯苯那敏的浓度采用HPLC-MS/MS测定,比较2组主要药动学参数的差异,评价中药成分对化药药动学参数的影响。结果试验制剂与参比制剂单次及多次给药后的药动学参数包括AUC0^t、Cmax、tmax间差异均无统计学意义(P>0.05)。结论感冒灵颗粒中的中药成分对各化药成分在人体的药动学无明显影响,其组方在药动学方面具有合理性。     

Lack of effect of paracetamol on the pharmacokinetics and metabolism of codeine in man

Summary Plasma and urine concentrations of codeine and its measurable metabolites were determined by HPLC in six healthy subjects after a single 30 mg oral dose of codeine either alone or after 7 doses of 1 g paracetamol 8 hourly.After codeine alone, the t_1/2 (h), AUC (mol·l^–1·h) and CL_R (ml·min^–1) for codeine were 2.2, 0.81, and 252 respectively. These were not significantly altered by paracetamol: 2.2, 0.84, and 291 respectively.For codeine-6-glucuronide the values were 2.4, 22.0, and 29.7 respectively. These were not significantly different from those after codeine plus paracetamol: 2.4, 21.9, and 39.6. There were no significant differences between the two treatments in the apparent partial clearances (ml·min^–1) of codeine to morphine (88 codeine alone, 70 codeine plus paracetamol), to norcodeine (71 codeine alone, 88 codeine plus paracetamol), and to codeine-6-glucoronide (820 codeine alone, 1022 codeine plus paracetamol).The urinary excretion of codeine-6-glucuronide, morphine, norcodeine, and codeine were not significantly different between the two treatments.     

Effects of imatinib mesylate on the pharmacokinetics of paracetamol (acetaminophen) in Korean patients with chronic myelogenous leukaemia

AIMS

The major objective of the present study was to investigate the effect of imatinib on the pharmacokinetics of paracetamol in patients with chronic myelogenous leukaemia (CML).

METHODS

Patients (n= 12) received a single oral dose of acetaminophen 1000 mg on day 1 (control). On days 2–8, imatinib 400 mg was administered daily. On day 8 (treatment), another 1000 mg dose of paracetamol was administered 1 h after the morning dose of imatinib 400 mg. Blood and urine samples were collected for bioanalytical analyses.

RESULTS

The area under the plasma concentration–time curve (AUC) for paracetamol, paracetamol glucuronide and paracetamol sulphate under control conditions was similar to that after treatment with imatinib; the 90% confidence interval of the log AUC ratio was within 0.8 to 1.25. Urinary excretion of paracetamol, paracetamol glucuronide and paracetamol sulphate was also unaffected by imatinib. The pharmacokinetics of paracetamol and imatinib in Korean patients with CML were similar to previous pharmacokinetic results in white patients with CML. Co-administration of a single dose of paracetamol and multiple doses of imatinib was well tolerated and safety profiles were similar to those of either drug alone.

CONCLUSIONS

The pharmacokinetics of paracetamol and its major metabolites in the presence of imatinib were similar to those of the control conditions and the combination was well tolerated. These findings suggest that imatinib can be safely administered with paracetamol without dose adjustment of either drug.     

高效液相色谱法测定对乙酰氨基酚的血药浓度及其生物利用度

目的 :建立高效液相色谱 (HPLC)法测定对乙酰氨基酚血药浓度的方法并对其分散片的生物利用度进行研究。方法 :以HPLC外标法测定人血浆中对乙酰氨基酚的浓度 ,流动相为甲醇 /乙腈 /水 (5∶5∶90 ) ,紫外吸收波长为 2 37nm。 12名健康志愿者服药后 ,依据对乙酰氨基酚分散片和对照片经时血药浓度 ,研究了 2种制剂相对生物利用度。结果 :本法对血浆中药物的最低检测浓度为 0 1μg·mL-1,线性范围为 0 2～ 18 0 μg·mL-1,回收率 >90 % ,日内RSD为 0 71%～ 1 6 5 % ,日间RSD为0 77%～ 4 41%。按AUC0→∞ 计算出对乙酰氨基酚分散片的相对生物利用度为 (10 7 8± 14 3) %。结论 :本法简便快速 ,可用于临床血药浓度测定。 2种对乙酰氨基酚制剂具有生物等效性。     

HPLC法测定腰息痛胶囊中对乙酰氨基酚含量

目的　测定腰息痛胶囊中对乙酰氨基酚含量。方法　样品用甲醇超声波一次性提取后 ,用 2 0 %甲醇稀释 ;采用HPLC法 ,以HypersilC18(BDS)为色谱柱 (2 0 0mm× 4.6mm) ,以甲醇 水 (2 0 ∶80 )为流动相 ,检测波长为 2 49nm。结果　对乙酰氨基酚添加回收率为 98.1% ,RSD为 0 .9% (n =5 ) ;检测限 (S/N =3)为 3.6× 10 -11g。结论　本法样品前处理简便 ,选择性强 ,灵敏度高 ,重现性好     

HPLC法测定氨酚咖黄烷胺片中对乙酰氨基酚和咖啡因的含量

目的建立氨酚咖黄烷胺片中对乙酰氨基酚和咖啡因的含量测定方法。方法采用Hypersil BDS C18色谱柱（150 mm×4.6 mm,5μm）,以甲醇-水（30∶70）为流动相,流速为1.0 ml·min^-1,检测波长为270 nm。结果对乙酰氨基酚在120.06～280.13 mg·L^-1范围内线性关系良好,r=0.999 8,平均回收率为99.89%,RSD=0.23%;无水咖啡因在7.24～16.89 mg·L^-1范围内线性关系良好,r=0.9997,平均回收率为99.70%,RSD=0.50%。结论本法操作简便、准确、快捷,可用于该产品的质量控制。     

反相高效液相色谱法测定对乙酰氨基酚血药浓度

建立了反相高效液相色谱法测定对乙酰氨基酚血浆中浓度的方法。方法使用YWGC18柱（4．6×250mm，10μm）；流动相为甲醇：醋酸－醋酸钠：二乙胺（20：80：0．5）；以茶碱为内标物；血清处理用甲醇沉淀蛋白；紫外检测波长244nm；流动相流速1．5ml／min；最低检出浓度0．05μg／ml。对乙酰氨基酚血药浓度在0．25~25μg／ml范围内线性关系良好（r＝0．9999）。本方法适用于对乙酸氨基酚的血药浓度测定。     

HPLC法测定复方对乙酰氨基酚片中对乙酰氨基酚、乙酰水杨酸及咖啡因的含量

目的:采用高效液相色谱法测定复方对乙酰氨基酚片中对乙酰氨基酚、乙酰水杨酸及咖啡因的含量。方法:采用 Li-chrospher C_(18)(5 μm,4.6 mm×250 mm)色谱柱,以甲醇-水-冰醋酸(40:60:0.3)为流动相,流速1.0 mL·min~(-1),检测波长272 nm,柱温35℃。结果:对乙酰氨基酚线性范围为19.93～199.32μg·mL~(-1)(r=0.9998),平均回收率(n=9)为99.2%;乙酰水杨酸线性范围为36.00～359.96μg·mL~(-1)(r=0.9999),平均同收率(n=9)为99.7%;咖啡因线性范围为4.90～49.04μg·mL~(-1)(r=0.9998),平均同收率(n=9)为98.8%。结论:方法简使,结果准确,适用于该产品的质量控制。     

高效液相色谱法测定人血浆对乙酰氨基酚浓度

目的建立血浆中对乙酰氨基酚的高效液相色谱检测法.方法经过乙醚为溶剂的液相提取,采用高效液相色谱法和紫外检测.结果血浆中对乙酰氨基酚能很好分离,无血浆内源物干扰,最低检测浓度为0.05 mg·L-1,对乙酰氨基酚在0.05～5.0 mg·L-1范围之间线性良好(r=0.999,P＜0.01),提取回收率在70%以上,相对回收率在90%附近,日间、日内变异系数均小于10%.结论该实验建立的血浆中对乙酰氨基酚HPLC检测法,符合生物样品分析要求.     

RP-HPLC测定速感宁胶囊中对乙酰氨基酚的含量

目的建立测定速感宁胶囊中对乙酰氨基酚含量的反相高效液相色谱方法。方法用Hypersil Kromasil C18色谱柱,流动相为甲醇-水-冰醋酸（20：80：0．5）,检测波长245nm,流速1．0ml·min^-1。结果对乙酰氨基酚的线性范围为0．3048～1．524mg·L^-1（r=0．9996）,平均回收率为98．94％,RSD为0．24％（n=6）。结论该方法专属性强、操作简便。     

氨酚曲马多片的镇痛作用

氨酚曲马多片（及通安）是一种新型镇痛药，为曲马多37．5mg和对乙酰氨基酚325mg组成的复方制剂。它能通过多种途径抑制疼痛，广泛用于中度疼痛的治疗。其镇痛效果优于单独使用两种单组分镇痛药物的效果，同时由于该复方制剂中每种药物成分的给药剂量较单独使用时低，从而减少了不良反应。现对其药效学、药动学、临床应用及不良反应做一介绍。     

氨咖黄敏胶囊中对乙酰氨基酚含量3种测定方法的比较

目的筛选测定氨咖黄敏胶囊中对乙酰氨基酚含量的最佳方法.方法对5批不同厂家的样品,分别采用高效液相色谱法(HPLC)、紫外分光光度法及亚硝酸钠法测定其中的对乙酰氨基酚含量,重点建立对乙酰氨基酚的HPLC含量测定方法,并对3种方法加以比较.结果 HPLC法对乙酰氨基酚的线性范围为0.97～48.48 g·L-1,回收率为99.4%～100.2%,RSD为0.3%.结论 HPLC法专属性强,灵敏、准确,可用于氨咖黄敏胶囊中对乙酰氨基酚的质量控制.     

氨咖黄敏胶囊中对乙酰氨基酚和咖啡因的人体药动学

目的研究氨咖黄敏胶囊中对乙酰氨基酚和咖啡因的人体药动学。方法本试验采用HPLC法测定了18名健康男性受试者口服氨咖黄敏胶囊后不同时刻血浆中对乙酰氨基酚和咖啡因的浓度，用31：97软件拟合房室模型并求出主要药动学参数。结果受试者口服含对乙酰氨基酚750mg和咖啡因45mg的氨咖黄敏胶囊制剂后，血浆中对乙酰氨基酚的tmax为（1．03±0．76）h，ρmax为（12．00±3．10）mg·L^-1，t1/2为（4．33±1．18）h，用梯形法计算AUC0→t为（52．51±16．81）mg·h·L^-1，AUC0→∞为（54．34±17．72）mg·h·L^-1；血浆中咖啡因的tmax为（0．89±0．50）h，ρmax为（1．290±0．379）mg·L^-1，t1/2为（5．37±2．15）h，用梯形法计算AUC0→t为（7．19±3．03）mg·h·L^-1，AUC0-∞。为（8．26±3．69）mg·h·L^-1。结论对乙酰氨基酚在人体内符合二房室模型，咖啡因在人体内符合一房室模型。     

LC-MS/MS法测定复方氯扑伪麻缓释片中主要成分的血浓度及其药动学

目的评价复方氯扑伪麻缓释片中的氯雷他定、对乙酰氨基酚和伪麻黄碱的药动学特点。方法采用LC-MS/MS法测定血浆中的氯雷他定、对乙酰氨基酚和伪麻黄碱浓度并用非房室模型计算药动学参数。结果8名受试者口服单剂量的复方氯扑伪麻缓释片后氯雷他定、对乙酰氨基酚和伪麻黄碱的AUC_(0→t)分别为:(18.04±13.81)、(26 455.42±5 245.72)、(3 703.16±487.26)μg·h·L~(-1);ρ_(max)分别为(6.81±4.98)、(3 918.75±816.17)和(423.63±49.55)μg·L~(-1);t_(max)分别为(0.91±0.30)、(4.13±1.13)和(5.25±0.89)h;t_(1/2)分别为(3.71±1.72)、(5.34±2.02)和(11.81±5.08)h。多剂量给药后氯雷他定、对乙酰氨基酚和伪麻黄碱的AUC~(ss)分别为:(63.26±39.58)、(49 226.51±11 103.51)和(11 046.73±12 642.36)μg·h·L~(-1);ρ_(max)分别为(6.36±3.31)、(5 733.75±1 099.06)和(576.38±136.48)μg·L~(-1);ρ_(min)分别为(1.08±0.74)、(1 890.63±350.06)和(247.88±71.35)μg·L~(-1);t_(max)分别为(1.13±0.55)、(2.31±0.88)和(3.38±1.06)h;ρ_(av)分别为(3.72±2.00)、(3 812.19±576.16)和(412.13±94.01)μg·L~(-1);DF分别为(143.02±26.11)、(99.54±21.74)和(80.07±18.09)%。结论单剂量和多剂量给药后,氯雷他定、对乙酰氨基酚和伪麻黄碱的药动学参数基本没有明显变化。