丙磺舒对大鼠体内头孢克罗药动学的影响

目的 :观察不同剂量丙磺舒对大鼠体内头孢克罗药动学的影响。方法 :大鼠 2 4只随机分成 4组 ,Ⅰ组 :单用头孢克罗 10 0mg·kg-1;Ⅱ组 :头孢克罗 10 0mg·kg-1联用丙磺舒 30 0mg·kg-1;Ⅲ组 :头孢克罗 10 0mg·kg-1联用丙磺舒 6 0 0mg·kg-1;Ⅳ组 :头孢克罗 10 0mg·kg-1联用丙磺舒 90 0mg·kg-1。各组动物灌胃给药后不同时间取血 ,HPLC法测头孢克罗血药浓度 ,DAS程序计算药动学参数。结果 :联用剂量在 30 0～ 6 0 0mg·kg-1范围内 ,随丙磺舒联用剂量增大 ,头孢克罗的Cmax、AUC增高而CL F、V F减少 ;当丙磺舒联用剂量达 90 0mg·kg-1时 ,头孢克罗的Cmax反而降低 ,而AUC、CL F则稳定于联用丙磺舒6 0 0mg·kg-1时的水平。结论 :丙磺舒可明显改变头孢克罗的药动学 ,在本实验剂量范围内其影响程度与丙磺舒剂量有关 ,随丙磺舒联用剂量增大 ,头孢克罗的Cmax先升高后降低 ,该现象可能与大剂量丙磺舒抑制头孢克罗的肠吸收有关。     

氨苄西林丙磺舒胶囊的HPLC测定

建立了HPLC法测定氨苄西林丙磺舒胶囊的含量.采用C18色谱柱,以甲醇-0.02mol/L磷酸二氢钾溶液(用磷酸调至pH 3.0)(50:50)为流动相,检测波长232nm,流速lml/min.氨苄西林和丙磺舒分别在80～800μg/ml(r=0.9992)和22～220μg/ml(r=0.9996)范围内线性关系良好,平均回收率分别为99.2%和99.5%.     

氨苄青霉素/丙磺舒胶囊的临床疗效与安全性研究

采用随机对照多中心临床研究 ,使用氨苄青霉素 /丙磺舒胶囊治疗急性细菌性感染患者 10 4例。其中 5 0例与进口氨苄青霉素胶囊治疗同类患者 5 0例进行随机对照试验 ;5 4例为开放性试验。试验组和对照组痊愈率与有效率均无显著性差异。试验组细菌清除率为 86 7% ,与对照组虽无显著性差异 ,但其耐药率为 7 1% ,低于对照组。不良反应发生率为 5 0 %。结果表明氨苄青霉素 /丙磺舒胶囊是一高效、安全的抗菌素。     

Sulfate Homeostasis. IV. Probenecid-Induced Alterations of Inorganic Sulfate in Rats

Homeostasis of inorganic sulfate is maintained by the capacity-limited renal reabsorption of sulfate in the proximal tubule. The purpose of the present investigation was to determine if probenecid, the classical inhibitor of renal organic anion secretion, may affect sulfate renal clearance. Two groups of rats were administered in a randomized crossover design, an i.v. bolus dose (20.6 or 92.4 mg/kg) and 4-hr infusion (0.28 or 0.59 mg/min/kg) of probenecid or vehicle, and blood and urine samples were collected. At a steady-state serum concentration of 0.45 mM, probenecid had no significant effect on the serum concentrations or renal clearance of inorganic sulfate, whereas at a serum concentration of 1.4 mM, probenecid treatment caused a significant decrease in serum sulfate concentrations (0.57 ± 0.11 vs 0.96 ± 0.19 mM in controls, mean ± SD, n = 6, P < 0.001) due to an increase in the renal clearance of sulfate (3.88 ± 1.18 vs 2.13 ± 0.84 ml/min/kg in controls, P < 0.01). The fraction of the filtered sulfate that was reabsorbed was significantly decreased (0.38 ± 0.23, vs 0.74 ± 0.09 in controls, P < 0.01). Therefore, probenecid treatment results in the inhibition of the renal reabsorption of inorganic sulfate in rats in vivo.     

RP-HPLC测定氨苄西林丙磺舒胶囊中的有关物质

目的建立氨苄西林丙磺舒胶囊有关物质的RP-HPLC梯度洗脱方法。方法色谱柱为十八烷基硅烷键合硅胶柱;流动相A为2 mol/L醋酸溶液-0.2 moL/L磷酸二氢钾溶液-乙腈-水(0.5:50:50:900);流动相B为2 moL/L醋酸溶液-0.2 mol/ L磷酸二氢钾溶液-乙腈-水(0.5:50:400:550),流速为1 ml/min,线性梯度洗脱;检测波长为254 nm,柱温40℃,进样器15℃,进样量为20μl。结果该方法能专属、准确地测定氨苄西林丙磺舒胶囊中的有关物质。结论本色谱条件适合氨苄西林丙磺舒胶囊有关物质的测定,可纳入氨苄西林丙磺舒胶囊质量标准。     

氨苄西林丙磺舒胶囊剂人体生物等效性研究

目的比较两种氨苄西林丙磺舒胶囊的药代动力学参数及人体生物等效性。方法20例健康男性受试者随机交叉口服受试制剂及参比制剂0．75g，采用高效液相色谱法分别测定血浆中氨苄西林和丙磺舒的质量浓度，利用3P97生物等效性程序自动进行相对生物利用度（F）和生物等效性分析。结果受试制剂和参比制剂中氨苄西林药-时曲线下面积（AUC0→t）分别为（19．527±5．835）μg·h／L和（18．464±5．807）μg·h／L，峰浓度（Cmax）分别为（5．465±1．460）μg／L和（5．360±1．936）μg／L，达峰时间（Tmax）分别为（2．250±0．866）h和（2．350±1．027）h，半衰期（t1/2）分别为（1．188±0．364）h和（1．203±0．382）h；受试制剂和参比制剂中丙磺舒AUG0→t分别为（92．964±17．176）μg·h／L和（87．558±22．587）μg·h／L，Cmax分别为（13．635±2．308）μg／L和（13．931±2．976）μg／L，Tmax分别为（2．450±1．145）h和（2．650±0．961）h，t1/2分别为（3．747±1．749）h和（3．784±0．711）h。以AUG0→t计算，氨苄西林的F平均为（112．7±38．1）％，丙磺舒的F平均为（112．0±34．0）％。结论两种氨苄西林丙磺舒胶囊具有生物等效性。     

丙磺舒对头孢克罗肠道吸收的影响(英文)

目的:研究不同剂量丙磺舒联用对头孢克罗肠道吸收的影响及其可能机制。方法:(1)药代动力学试验:头孢克罗(100mg/kg)对大鼠静脉给药,分别与不同剂量丙磺舒(0、300、600、900mg/kg)联用,HPLC监测用药后不同时间的血药浓度,DAS软件计算头孢克罗的药代动力学参数。(2)肠道吸收试验:头孢克罗(30μg/mL)分别与不同剂量丙磺舒(0、90、180、270μg/mL)联用,对大鼠在体肠回流给药,给药后不同时间采样,HPLC测定灌流液中头孢克罗浓度的经时变化。结果:(1)头孢克罗静脉给药的血药浓度-时间曲线呈二室开放模型;在试验剂量范围内,随丙磺舒联用剂量增大,头孢克罗的血药浓度呈剂量依赖性增高;AUC与丙磺舒联用剂量呈正相关(r=0.997),而Cl、Vd及V1与丙磺舒联用剂量呈负相关(r=-0.837,-0.817及-0.888)。(2)大鼠在体肠回流实验表明,不同剂量丙磺舒联用对头孢克罗肠道吸收影响的程度不同,当丙磺舒联用剂量达270μg/mL水平时,灌流液内头孢克罗的留存率明显增高。结论:与适量丙磺舒联用,头孢克罗分布容积及血浆清除率降低,血药浓度增高;而与大剂量丙磺舒联用则明显延缓或抑...     

Potentiation of barbiturate- and halothane-induced hypnosis after probenecid or sulfinpyrazone pretreatment

The uricosuric agent, probenecid, when administered prior to systemic administration of pentobarbital led to a decreased latency, to loss of righting reflex and to a potentiation of the duration of hypnosis. This potentiation was dose-related and doses of probenecid below 50mg/kg (i.p.) were without effect. Pretreatment of rats with sulfinpyrazone, another uricosuric agent, yielded similar results. Pre-treatment of animals with probenecid shortened the latency to onset of hypnosis induced by halothane (i.p.) and increased the duration of loss of righting reflex, 3-fold. Both sulfinpyrazone and probenecid, administered prior to 1.0% inhalation halothane exposure, shortened the latency to onset of hypnosis in doses as small as 10mg/kg, much less than the doses required to affect significantly pentobarbital-induced hypnosis. The results, as yet, do not indicate a plausible mechanism of action, but do expose a potentially useful drug interaction which may be of clinical use.     

The influence of allopurinol and size of dose on the metabolism of phenylbutazone in patients with gout

Summary Administration of allopurinol 300 mg/day produced minimal changes in the disappearance of phenylbutazone in each of five subjects following single doses (6 mg/kg) in clinical range and caused some prolongation (21%, 52%) of drug half-lives in two of six subjects after single small doses (0.5 mg/kg); mean half-life was not significantly altered by allopurinol at either dose level (means of 52 versus 48 at 0.5 mg/kg and 68 versus 70 h at 6 mg/kg). Size of dose altered half-life when phenylbutazone was used alone; three subjects showed considerably longer half-lives at the higher dose (86 versus 47, 91 versus 41, 65 versus 38 h). Allopurinol caused a greater than 50% prolongation of half-lives in two of five subjects who received single 0.5 g doses of probenecid. These preliminary data do not indicate a need to change the dose of phenylbutazone when subjects are receiving allopurinol.     

Serum concentrations of ampicillin and probenecid and ampicillin excretion after repeated oral administration of a pivampicillin-probenecid salt (MK-356)

Summary Twenty male volunteers received oral doses (2100, 1050, and 525 mg) of a pivampicillin-probenecid salt in a 1 to 1 molar ratio (MK-356) at 12 hour intervals. After each dose peak serum concentrations of probenecid were observed 2 hours later than peak concentrations of ampicillin. Following the first dose of MK-356 the apparent elimination rate of ampicillin was dose-dependent and did not follow first order kinetics, as it showed a longer apparent half life after a higher dose. An equal dose of MK-356 administered 12 hours later caused an increase in the peak serum ampicillin level greater than expected from the concentration of ampicillin after the preceding dose. In twelve male volunteers who received at random 525 mg of MK-356 or 350 mg of pivampicillin, each three times daily for 4 days, the areas under the ampicillin concentration curve were the same after the first or last dose of either drug. When 2100 or 1050 mg of MK-356 was taken as an initial dose, 30 to 40 per cent of the ampicillin was recovered from urine in the ensuing 12 hours. The results indicate that when at least 400 mg probenecid was coadministered twice daily with 700 mg pivampicillin (MK-356), the peak serum concentrations of ampicillin were increased and its elimination rate slowed following successive doses.