哌拉西林钠对甲磺酸帕珠沙星在大鼠体内药代动力学的影响

目的研究哌拉西林钠对甲磺酸帕珠沙星在大鼠体内药代动力学的影响。方法 12只健康雄性SD大鼠随机分成2组(分别为单独和联合给药组),用HPLC法测定血浆中甲磺酸帕珠沙星的浓度。结果单独用药与联合用药组ρmax分别为(33.54±4.68)和(37.83±3.43)mg.L-1,AUC0-t分别为(43.32±15.91)和(41.98±9.19)mg.h.L-1,t1/2分别为(1.00±0.31)和(0.80±0.24)h,无显著性差异(P>0.05)。结论与哌拉西林钠联合用药后甲磺酸帕珠沙星在大鼠体内的药动学参数均不存在显著性差异。     

国产甲磺酸帕珠沙星注射液健康志愿者多剂连续给药药动学研究

目的:研究国产甲磺酸帕珠沙星注射液多次连续给药在健康人体内的药动学特点.方法:12例健康志愿者静滴甲磺酸帕珠沙星注射液500 mg,bid,连续5 d,并采用反相高效液相色谱法测定血药浓度数据,用DAS软件计算主要药动学参数.结果:静滴甲磺酸帕珠沙星药动学特点符合开放二室模型,第1次单次给药和最后1次给药的主要药动学参数如下:平均峰浓度分别为(10.86±2.04)和(11.72±1.82)mg·L-1,平均稳态药一时曲线下面积AUC0～∞分别为(18.29±2.36)和(19.22±2.80)mg·h·L-1,t1/2β分别为(1.64±0.27)和(1.82±0.34)h.结论:连续给药帕珠沙星5 d,受试者耐受良好,药动学过程符合二室模型,多次给药体内无蓄积.     

甲磺酸帕珠沙星原料药的急性毒性作用研究

目的 研究甲磺酸帕珠沙星原料药的急性毒性作用,指导临床安全用药.方法 按照〈化学药物急性毒性试验技术指导原则〉中方法进行试验.结果 甲磺酸帕珠沙星原料药小鼠一次性灌胃最小致死量（MLD）大于5000mg/kg,小鼠静脉注射半数致死量（LD50）为439.35mg/kg,95%可信限为399.99～482.58 mg/kg.结论 甲磺酸帕珠沙星毒性小,使用安全范围大.     

甲磺酸帕珠沙星注射液单次给药在人体内的药物动力学研究

目的建立测定甲磺酸帕珠沙星血浆药物浓度的HPLC-UV检测法,研究国产甲磺酸帕珠沙星氯化钠注射液在人体内的药物动力学。方法12名健康志愿受试者单次静滴甲磺酸帕珠沙星氯化钠注射液500 mg,以盐酸芦氟沙星为内标,测定血浆中帕珠沙星的浓度,用DAS 1.0软件处理经时血药浓度数据,计算主要药物动力学参数。结果单次静滴甲磺酸帕珠沙星氯化钠注射液500 mg后,于给药后0.50 h达到峰浓度9.83±2.52 mg.L-1,AUC0-t为18.99±4.15 mg.h.L-1,T1/2β为2.67±0.31 h,Cl/F和V/F分别为23.73±3.81 L.h-1和1.16±0.31 L.kg-1。结论单次静滴甲磺酸帕珠沙星氯化钠注射液的体内过程符合二室开放模型;除AUC外,男、女受试者的其余药动学参数比较,差异无统计学意义。     

高效液相色谱法同时测定大鼠甲磺酸帕珠沙星和头孢哌酮的血浆浓度

目的建立大鼠甲磺酸帕珠沙星和头孢哌酮血浆浓度的反相高效液相色谱分析方法,为研究药物相互作用及联合用药后的药动学参数提供测定方法.方法用高氯酸沉淀血浆蛋白,采用Hypersil BDS C18柱(4.6 mm×150 mm,5 μm),流动相为乙腈-磷酸三乙胺水溶液(0.5%磷酸,1%三乙胺)(17∶83,v/v),检测波长为245 nm.结果甲磺酸帕珠沙星在0.1～100mg·L-1,头孢哌酮在0.5～500 mg·L-1,峰面积与浓度呈良好线性关系(r1=0.999 6,r2=0.999 7),平均绝对回收率为99.3%和105.4%,平均相对回收率为104.2%和98.6%,日内、日间RSD均小于10%.结论本方法操作简便,专属性及重现性好,适用于进一步的药物相互作用及体内药动学研究.     

甲磺酸帕珠沙星的人体药动学

目的:研究甲磺酸帕珠沙星在健康人体内的药动学特征。方法:12名健康志愿者(男女各6名)单剂量和多剂量静脉滴注甲磺酸帕珠沙星氯化钠注射液300mg,滴注时间30min。血浆用20%高氯酸水溶液沉淀蛋白,上清液直接用高效液相色谱-荧光检测血浆中帕珠沙星药物浓度。结果:最小检测限小于0.028mg.L-1,提取回收率大于90%,日内、日间变异(RSD小于10%)。静脉滴注甲磺酸帕珠沙星在健康人体内的药动学特征用3P97程序拟合为二房室模型,其主要药动力学参数单剂量时和多剂量时的Cmax,t1/2β,AUC0-t,AUC0-∞,Vc和CL分别为(7.2±0.8)mg.L-1和(7.3±0.8)mg.L-1,(2.04±0.17)h和(2.24±0.23)h,(14.0±1.5)mg.L.h-1和(14.3±1.5)mg.L.h-1,(13.1±1.5)mg.L.h-1和(13.3±1.2)mg.L.h-1,(27.2±4.6)L和(25.3±8.8)L,(22.1±2.6)L.h-1和(23.7±2.1)L.h-1。单剂量时和多剂量间的药动学参数,除了t1/2β和MRT有性别差异外,其余无明显差异。结论:静脉滴注甲磺酸帕珠沙星后无论单剂量和多剂量的药动学参数基本一致,说明连续300mg,bid,静脉滴注5d体内无明显累积,药动学参数如t1/2β,MRT可能存在性别差异,其原因尚不清。     

甲磺酸帕珠沙星氯化钠注射液健康志愿者单剂给药药动学

目的研究健康志愿者静脉滴注单剂甲磺酸帕珠沙星氯化钠注射液后药动学特征,为该药Ⅱ期临床试验提供依据。方法采用2剂量2周期交叉试验设计。10名健康受试者单剂静脉滴注甲磺酸帕珠沙星氯化钠注射液300、500mg,HPLC法测其血清、尿药物浓度。结果受试者静脉滴注甲磺酸帕珠沙星氯化钠注射液后,人体耐受良好,体内过程符合二室开放模型。主要药动学参数与给药剂量呈线性关系,cmax分别为8.3和11.07μg/ml,AUC0-∞分别为13.66和24.04μg.h/ml,V值分别为28.9和40L,t1/2β分别为1.77和2.27h,36h尿药累积回收率约为79%。结论甲磺酸帕珠沙星氯化钠注射液静脉滴注血峰浓度高,组织分布较广,消除半衰期短,300mg每日2次可用于治疗敏感菌感染。     

小儿支气管肺炎常用4种药物治疗方案的成本-效果分析

目的:分析比较头孢呋辛、头孢哌酮-舒巴坦钠、头孢呋辛与阿奇霉素、头孢哌酮-舒巴坦钠与阿奇霉素联用针对支气管肺炎患儿的4种常见药物治疗方案的成本-效果指标,探究方案中最优经济学特点的治疗方案.方法:选取2019年1月-12月间收治的116例小儿支气管肺炎患儿资料,按治疗药物的不同分为头孢呋辛组(21例)、头孢哌酮-舒巴坦钠组(21例)、头孢呋辛与阿奇霉素组(36例)和头孢哌酮-舒巴坦钠与阿奇霉素组(38例);采用药物经济学成本-效果分析(CEA)法,分析不同治疗方案的效果和成本之间的关系,评出最优的治疗方案.结果:小儿支气管肺炎的4种药物治疗方案的成本-效果(C/E)之比分别为37.68、38.48、32.38和46.21;头孢哌酮-舒巴坦钠与阿奇霉素联用治疗小儿支气管肺炎的成本高于头孢呋辛与阿奇霉素的联用,其增量C/E比为476.74(每增加1个治愈值所需的成本).结论:在4种药物治疗方案中,从成本-效果的角度考虑,采用头孢呋辛与阿奇霉素联用治疗小儿支气管肺炎是最理想的给药方案.     

头孢哌酮-舒巴坦与阿奇霉素联用对支原体肺炎患者伴细菌感染的临床疗效与安全性评价

目的:探究头孢哌酮-舒巴坦与阿奇霉素联用对支原体肺炎患者伴细菌感染的临床疗效与安全性。方法:选取2016年6月—2017年5月间收治的支原体肺炎伴细菌感染患者98例资料,按用药的不同分为阿奇霉素组和联用组,每组49例;阿奇霉素组患者给予阿奇霉素治疗,联用组患者在其基础上加用头孢哌酮-舒巴坦治疗,比较两组患者用药后的总有效率、不良反应发生率的差异。结果:联用组患者用药后的总有效率(93.88%)显著高于阿奇霉素组(77.55%)(P<0.05),用药期间不良反应发生率(8.16%)低于阿奇霉素组(14.29%)(P<0.05)。结论:头孢哌酮-舒巴坦与阿奇霉素联用于治疗支原体肺炎伴细菌感染患者的疗效较为确切,安全性较高。     

HPLC法测定甲磺酸帕珠沙星原料及其制剂含量

目的:采用高效液相色谱法测定甲磺酸帕珠沙星原料及其制剂含量.方法:Hypersil C18(5 μm,4.6 mm×250 mm)色谱柱,0.1%磷酸溶液(加磷酸氢二钾80.5 mg)-乙腈(85:15)为流动相,流速1.0ml·min-1,柱温30℃,检测波长243 nm.结果:甲磺酸帕珠沙星在5～500μg·ml-1内与峰面积呈良好的线性关系.甲磺酸帕珠沙星原料(3批)加样回收率99.2%甲磺酸帕珠沙星注射液加样回收率均值为100.1%;甲磺酸帕珠沙星氯化钠注射液加样回收率均值为99.7%.结论:采用HPLC测定原料及其制剂中甲磺酸帕珠沙星含量方法简便,结果可靠.     

Influence of cefoperazone and azithromycin on the pharmacokinetics of pazufloxacin in rats.

The effects of cefoperazone and azithromycin administered separately on the pharmacokinetics of pazufloxacin (PZFX) mesilate were investigated in rats. Animals were injected with cefoperazone at a high dose (180 mg/kg) or azithromycin at a dose of 45 mg/kg through the tail vein 10 min before intravenous (i.v.) administration of PZFX (45 mg/kg). Blood concentrations of PZFX were determined by HPLC. Parameters relating to the pharmacokinetic interaction between PZFX and cefoperazone or azithromycin were estimated by a two-compartmental model. The experimental results showed that the presence of azithromycin significantly delayed the t(1/2 beta) and mean residence time (MRT) of PZFX in the plasma. However, no significant changes between the control group and the cefoperazone-treated animals in the pharmacokinetic parameters of PZFX, such as t(1/2 beta), volume of distribution (Vd), area under the curve (AUC) and the clearance (Cl) were observed.     

5种方案治疗小儿肺炎的成本-效果分析

目的:评价5种方案治疗小儿肺炎的经济性。方法:采用回顾性研究和成本-效果分析方法,对阿莫西林钠/克拉维酸钾(A组)、头孢噻肟钠(B组)、头孢哌酮钠/舒巴坦钠(C组)、头孢呋辛钠(D组)、阿奇霉素(E组)治疗小儿肺炎的5种方案进行药物经济学评价。结果:A、B、C、D、E组有效率分别为80.43%、76.09%、65.12%、77.27%、91.30%,成本-效果比分别为1 595.06、1 225.38、1 669.69、1 284.83、697.84。结论:E组方案治疗小儿肺炎较佳。     

阿奇霉素联合头孢哌酮钠舒巴坦钠治疗老年肺炎的效果分析

目的 研究阿奇霉素联合头孢哌酮钠舒巴坦钠治疗老年肺炎的临床效果.方法 94例老年肺炎患者,根据治疗方式不同将其分为研究组与对照组,每组47例.对照组采用阿奇霉素进行治疗,研究组采用阿奇霉素联合头孢哌酮钠舒巴坦钠治疗.对比两组临床疗效、治疗期间不良反应发生情况、临床症状改善时间、治疗前后炎性因子指标.结果 研究组治疗总有...     

莫西沙星与阿奇霉素联合头孢哌酮/舒巴坦治疗社区获得性肺炎的疗效观察

目的:观察莫西沙星与抗菌谱相近的阿奇霉素联合头孢哌酮/舒巴坦治疗社区获得性肺炎的临床疗效和安全性。方法:收集66例社区获得性肺炎患者,以随机抽样法分为2组。实验组(33例)给予莫西沙星注射液0.4 g,qd,静脉滴注;对照组(33例)给予阿奇霉素0.5 g,qd,联合头孢哌酮/舒巴坦2.5 g,bid,静脉滴注。结果:疗程结束后,2组在临床疗效、细菌清除率、不良反应方面比较,差异均无统计学意义(P>0.05)。结论:莫西沙星治疗社区获得性肺炎疗效确切,安全性与阿奇霉素联合头孢哌酮/舒巴坦相似。     

Pharmacokinetics,Bioavailability, and Safety of Montelukast Sodium (MK-0476) in Healthy Males and Females

Purpose. The safety, tolerability, and pharmacokinetics of intravenous (i.v.) montelukast sodium (Singulair, MK-0476), and the oral bioavailability of montelukast sodium in healthy males and healthy females were studied. Methods. This was a two-part study. Part I was a four-period study in males of rising i.v. doses of montelukast sodium (3, 9, and 18 mg) administered as 15-minute constant-rate i.v. infusions (Periods 1–3), followed by a 10-mg oral tablet dose of montelukast sodium (Period 4) under fasting conditions. Part II was a four-period study in females of i.v. montelukast sodium (9 mg) infused over 15 and 5 minutes (Periods 5 and 6, respectively) or injected as a bolus over 2 minutes (Period 7), followed by a 10-mg oral tablet dose of montelukast sodium (Period 8). Plasma samples were collected and analyzed by HPLC. Results. In males (N = 6), as the i.v. dose of montelukast sodium increased from 3 to 18 mg, the area under the plasma concentration-time curve of montelukast sodium from time 0 to infinity (AUC) increased proportionately. The mean values of plasma clearance (CL), steady-state volume of distribution (V_ss), plasma terminal half-life (t_1/12), and mean residence time in the body (MRT^i.v.) of montelukast sodium were 45.5 ml/min, 10.5 1, 5.1 hr, and 3.9 hr, respectively, and remained essentially constant over the i.v. dosage range. Following oral administration of a 10-mg tablet of montelukast sodium, the AUC, maximum plasma concentration (C_max), time when C_max occurred (T_max), apparent t_1/12, mean absorption time (MAT), and bioavailability (F) of montelukast sodium averaged 2441 ng · hr/ml, 385 ng/ml, 3.7 hr, 4.9 hr, 3.4 hr, and 66%, respectively. Following i.v. administration of 9 mg of montelukast sodium to females (N = 6), the values of CL, V_ss, t_1/2, and MRT i.v. averaged 47.6 ml/min, 9.6 1, 4.5 hr, and 3.6 hr, respectively. Following oral administration of a 10-mg tablet to females, the mean AUC, C_max, T_max, apparent t_1/2, MAT and F were 2270 ng·hr/ml, 350 ng/ml, 3.3 hr, 4.4 hr, 2.6 hr, and 58%, respectively. These parameter values were similar to or slightly smaller than those in healthy males receiving the same i.v. and oral doses. Conclusions. The disposition kinetics of montelukast sodium were linear. Gender had little or no effect on the kinetics of montelukast sodium. Safety results from this study indicate that intravenous doses of montelukast sodium from 3 to 18 mg and a 10-mg oral dose are well tolerated.     

Bioequivalence studies of a new valproic acid delayed-release capsule and divalproex sodium delayed-release tablet

ABSTRACT

Objective: The study examined relative bioavailability of a novel valproic acid (VPA) delayed-release (DR) soft gelatin capsule formulation to divalproex sodium DR tablet under fasting conditions and the effect of food on the bioavailability of the VPA DR soft gelatin capsule.

Method: This open-label, randomized three-way crossover study enrolled 36 healthy non-smoking adult volunteers. Treatments included a single 500 mg divalproex sodium DR tablet, fasting; a single 500 mg VPA DR soft gelatin capsule, fasting; and, a single 500 mg VPA DR soft gelatin capsule 500 mg, non-fasting. Analysis of variance was performed on the pharmacokinetic parameters. The ratio of geometric means and corresponding 90% confidence intervals (CI) were calculated on ln-transformed data for the area under the serum concentration-time curve (µg-hr/mL) from time zero to the time of the last quantifiable concentration (t) (AUC_0–t), AUC_0–∞ and maximum plasma concentration (C_max). Bioequivalence was shown when 90% CIs were within the 80–125% range.

Results: All subjects completed the study. The 90% CIs of VPA DR soft gelatin capsules compared to divalproex sodium DR tablets were within the 80–125% limits for AUC_0–t, AUC_0–∞, and C_max. The time of maximum or peak concentration (T_max) of VPA DR soft gelatin capsules was 2.3 hours versus 3.7 hours with divalproex sodium DR tablets. AUC_0–t and AUC_0–∞ of VPA soft gelatin capsules were not affected in the non-fasting condition, but T_max occurred at 6.1 hours compared to 2.3 hours fasting. Eight subjects experienced a total of 10 adverse events; none were serious.

Conclusion: The VPA DR soft gelatin capsule formulation was shown to be bioequivalent to divalproex sodium DR tablet and no serious adverse events occurred. Because this was not a multiple-dose study, however, direct comparisons in chronic dosing were not possible. Administration with food affected rate but not extent of absorption of the VPA DR soft gelatin capsules, but comparisons with the reference product were not conducted under non-fasting conditions.     

Pharmacokinetics of pirmenol in young and elderly subjects

Summary The steady state pharmacokinetics of pirmenol was compared in twelve healthy young (aged 18 to 45 y) and 11 elderly subjects (over 65 y) subjects given pirmenol HCl 100 mg every 12 h for a total of 14 doses. In addition, the single-dose pharmacokinetics of pirmenol was determined following a 100 mg oral dose in the young subject group for comparison with the results of repeated administration.In the young subjects, the mean single-dose and steady-state CL_R of pirmenol were similar; however, Ae was 29 % higher and CL/f was 22 % lower at steady state than after the single dose. Steady-state (fourteenth dose) C_min, C_max, t_max, z, Ae, CL/f, CL_R and V values were similar in the young and elderly subjects.Based on pharmacokinetic considerations, the dosage of pirmenol is unlikely to differ in young and elderly subjects.     

Comparison of pharmacokinetic profile of levodopa throughout the day between levodopa/carbidopa/entacapone and levodopa/carbidopa when administered four or five times daily

Objectives

To compare plasma levodopa concentrations after repeated doses of levodopa/carbidopa/entacapone (LCE) and levodopa/carbidopa (LC).

Methods

Open-label, randomized, two-period, active-controlled, cross-over study with four dosing regimens: groups I and II (healthy volunteers and Parkinson’s disease patients) received levodopa 100 mg or 150 mg four times daily, respectively, and groups III and IV (healthy volunteers) received the same strengths of levodopa five times daily. Pharmacokinetic (PK) parameters determined for levodopa included C_min, C_max, C_max???C_min, AUC, t_1/2, and t_max.

Results

In healthy volunteers and PD patients, mean trough levels (C_min), C_max, and AUC of levodopa were, in general, significantly higher during LCE compared to LC administration. Compared to C_min, C_max, and AUC, differences between the treatments in variability of levodopa concentrations (C_max???C_min) were less consistent.

Conclusions

The present results on the differences in levodopa PK between LCE and LC provide a basis to evaluate the relationship of levodopa PK and the induction of motor complications in an on-going study in early Parkinson’s disease using similar dosing regimens.     

医院内获得性肺炎抗菌药物的疗效和安全性比较

目的:比较头孢唑肟钠/莫西沙星,头孢哌酮钠/舒巴坦钠和头孢唑肟钠治疗医院内获得性肺炎(HAP)的有效性和安全性.方法:203例HAP患者随机分为Ⅰ、Ⅱ、Ⅲ组.Ⅰ组患者给予盐酸莫西沙星注射液400 mg,qd;注射用头孢唑肟钠2~4 g,bid.Ⅱ组患者给予注射用头孢哌酮钠舒巴坦钠(2:1)1~2 g,bid.Ⅲ组患者给予注射用头孢唑肟钠2~4 g,bid.主要疗效指标是在治疗期结束后患者的临床症状,次要观察指标为不良反应和细菌学反应.结果:头孢唑肟钠/莫西沙星、头孢哌酮钠舒巴坦钠、头孢唑肟钠的临床有效率分别为91.9%、89.7%和78.7%.治疗结束后,头孢唑肟钠/莫西沙星和头孢哌酮钠舒巴坦钠对痰液细菌的清除率显著高于头孢唑肟钠.3组药物的不良反应无明显差异.与头孢唑肟钠单独用药相比,头孢菌素联合喹诺酮类或β-内酰胺酶抑制剂的抗菌疗效更佳.结论:头孢菌素联合喹诺酮类药物或β-内酰胺酶抑制剂可作为临床治疗HAP的优选用药方案.     

抗疟药咯萘啶在兔体内的药代动力学

本文报道抗疟药咯萘啶iv,im和ig给药后在兔体内的药代动力学。用NONLIN程序对血药—时间数据进行拟合。一次快速iv 6 mg/kg后的血药—时间过程符合线性三室开模型。药代动力学参数(±SD):t 1/2_β为59±10h;V_c2.418±0.287L/kg;V_d(ss),29±6 L/kg;总清除率Cl_T为0.442±0.131 L/kg·h。Im和ig给药后的动力学过程以线性二室开模型描述。im 6 mg/kg,吸收速率常数K_a为33.5±21.8 h^-1,t 1/2_β为52±8 h,吸收完全。Ig 30或60 mg/kg后的k_a为2.41±1.26 h^-1,t 1/2_β为55±5 h,吸收程度为34.6%。咯萘啶在血中呈不均一分布,im后1～96 h,球/浆浓度比为3～6。