硝酸铋与丙磺舒合用对顺铂肾毒性的防护作用

毒性剂量的顺铂（ＣＰ３０μｍｏｌ·ｋｇ－１ｉｐ）可引起血尿素氮（ＢＵＮ）升高。硝酸铋（ＢＮ）５μｍｏｌ·ｋｇ－１于ＣＰ前４８和２４ｈｓｅ，丙磺舒（Ｐｒｏ）７００μｍｏｌ·ｋｇ－１于ＣＰ前１５，１ｈ及ＣＰ后５ｈｉｇ，或ＢＮ与Ｐｒｏ二者半量合用，按上述给药，均能抑制ＣＰ引起的ＢＵＮ升高，尤以ＢＮ＋Ｐｒｏ组抑制作用显著。肾脏光镜和电镜标本显示，ＣＰ使肾小管受损严重；ＢＮ组，Ｐｒｏ组和ＢＮ＋Ｐｒｏ组均使ＣＰ引起的肾小管受损减轻，尤以ＢＮ＋Ｐｒｏ组减轻明显。ＢＮ２．５－２０μｍｏｌ·ｋｇ－１剂量依赖性地诱导小鼠肾脏金属硫蛋白合成。Ｐｒｏ可使ＣＰ后２４ｂ肾铂含量明显降低；Ｐｒｏ或Ｐｒｏ＋ＢＮ使尿铂累积排出量增加，血浆铂浓度降低。提示ＰＦＯ防护ＣＰ肾毒性与其减少肾铂分布，增加尿铂排出有关。     

丙磺舒对阿莫西林在家兔体内的药动学影响

目的:观察丙磺舒对阿莫西林在健康家兔体内药动学的影响.方法:采用微生物杯碟法测定兔血清中阿莫西林的浓度.结果:阿莫西林单剂量肌内注射后,吸收迅速,Tmax=(0.78±0.09)h,Cmax=(0.87±0.30)μg·mL-1,其代谢模型为一级速率一房室模型.当阿莫西林和丙磺舒等剂量伍用时丙磺舒对阿莫西林药动学参数的影响达到最大值:阿莫西林的t1/2由(2.06±0.09)h延长至(5.50±0.52)h,AUC由(4.07±0.05)μg·mL-1·h增加至(13.75±3.09)μg·mL-1·h,Cmax由(0.87±0.30)μg·mL-1增加至(6.30±1.46)μg·mL-1,且三者统计学差异极显著(P<0.01).结论:丙磺舒对阿莫西林的药动学参数的影响呈S型,当两者等剂量伍用时影响最大.     

Reduced gastrointestinal toxicity following inhibition of the biliary excretion of irinotecan and its metabolites by probenecid in rats

Purpose. To ameliorate the late-onset of severe gastrointestinal toxicity provoked by irinotecan (CPT-11), which may be related to the biliary excretion of CPT-11 and/or its metabolites. Methods. Effects of probenecid, an inhibitor of MRP2/ABCC2, on the biliary excretion and mucosal intestinal tissue concentration of CPT-11 and its metabolites were examined in rats. CPT-11-induced late-onset gastrointestinal toxicity was also evaluated. Results. Coadministration of probenecid reduced the biliary excretion of CPT-11, an active metabolite (SN-38) and its glucuronide by half with a concomitant increase in their plasma concentration. When the dose of CPT-11, in the presence of probenecid, was set at half that in its absence, the plasma SN-38 concentration was maintained at the same level as the control, whereas the mucosal intestinal tissue concentration of SN-38 was reduced. Under this condition, CPT-11-induced watery diarrhea, changes in intestinal marker enzymes and body weight reduction were much less in the probenecid-treated group, although the degree of bone marrow suppression was almost the same as that in the control. Conclusions. Coadministration of probenecid with a reduced dose of CPT-11 potently reduces both SN-38 exposure and CPT-11-induced late-onset toxicity in gastrointestinal tissues, possibly by inhibiting the biliary excretion of CPT-11 and/or its metabolites.     

三波长分光光度法测定安必欣胶囊的含量

 利用三波长分光光度法测定安必欣胶囊中丙磺舒和氨苄青霉素含量。两种组分的平均回收率和相对标准偏差分别是１０２．３％，ＲＳＤ０．２５％和１００．４％，ＲＳＤ０．４７％，ｎ＝５。此种方法操作简单，结果满意.     

Effects of probenecid on enprofylline kinetics in man

Summary Enprofylline 1 mg/kg, a new potent antiasthmatic xanthine derivative, which is mainly eliminated by renal excretion, was given intravenously to 6 normal subjects with and without oral pretreatment with 1 g probenecid. The latter caused a drop in the average total body clearance of enprofylline from 21 to 9.8 l/h, and in the average renal clearance from 17 to 8.0 l/h. The average half-life increased from 1.8 to 3.0 h. The volumes of distribution, V_z and V_ss, both fell by about 25%, indicating that probenecid had restricted the distribution of enprofylline in the body. The plasma protein binding of enprofylline was not altered by probenecid. The results confirm the opinion that active tubular secretion accounts for a large proportion of the total elimination of enprofylline.     

Kynurenine in combination with probenecid mitigates the stimulation-induced increase of <Emphasis Type="Italic">c-fos</Emphasis> immunoreactivity of the rat caudal trigeminal nucleus in an experimental migraine model

Summary Nitroglycerin, often used as a migraine model, results in increased number of c-fos immunoreactive secondary sensory neurons in the caudal trigeminal nucleus. Since synapses between first- and second-order trigeminal neurons are mediated by excitatory amino acids, NMDA receptors are presumably inhibited by kynurenic acid, the only known endogeneous NMDA receptor antagonist. Although kynurenic acid does not cross the BBB, its precursor, kynurenine, if combined with probenecid, crosses it readily. Systemic kynurenine + probenecid treatment significantly diminishes nitroglycerin-induced increase of c-fos immunoreactivity in the brainstem.     

不同剂量丙磺舒对头孢克罗药物动力学的影响

目的 :观察不同剂量丙磺舒 (Pro)对头孢克罗 (Cef)药动学的影响 ,为两者联用提供依据。方法 :家兔 30只随机分成 5组 ;Cef 5 0mg·kg- 1组 ,Cef5 0mg·kg- 1+Pro 5 0mg·kg- 1组 ,Cef 5 0mg·kg- 1+Pro 10 0mg·kg- 1组 ,Cef 5 0mg·kg- 1+Pro2 0 0mg·kg- 1组 ,Cef 2 5mg·kg- 1+Pro 10 0mg·kg- 1组。灌胃给药后于不同时间股静脉取血 ,HPLC法测定Cef血药浓度 ,NDST程序计算药动学参数。结果 :在给予Cef 5 0mg·kg- 1条件下 ,随Pro联用剂量的增大 ,Cef的Cmax、AUC增高而Cl/F、V/F减少 ;Cef2 5mg·kg- 1+Pro 10 0mg·kg- 1组各参数 (除Cl/F外 )与Cef 5 0mg·kg- 1组差异不显著。结论 :Pro可明显改变Cef的药动学 ,在实验剂量范围内其影响程度与丙磺舒剂量有关。Cef 2 5mg·kg- 1联用Pro10 0mg·kg- 1可产生Cef 5 0mg·kg- 1的血药水平。     

Non-linear elimination and protein binding of probenecid

Summary Six healthy volunteers were given probenecid 0.5, 1 and 2 g p.o. and 0.5 g i.v. The protein binding of probenecid at different concentrations in human plasma was estimated by equilibrium dialysis. The free fraction was found to increase nonlinearly with increasing total probenecid concentration, up to a maximum free fraction of 26%. The plasma concentration-time data after the oral doses were described by a one-compartment open model with first-order absorption and Michaelis-Menten elimination. The mean absorption rate constant 0.0072 min^–1 was dose-independent, and the maximal rate of elimination (mean 1429 µg/min) did not differ between doses whether calculated from the total or free concentrations. The Michaelis-Menten constant decreased significantly from 67.1 to 55.5 µg/ml as the dose increased from 1 g to 2 g, while the unbound Michaelis-Menten constant remained unchanged. The elimination of probenecid after the 0.5 g dose was in the linear region of the Michaelis-Menten elimination when calculated from the total and the free concentrations. The volume of distribution increased only slightly from 9.5 to 11.4 l as the dose increased from 0.5 to 2 g, but the unbound volume of distribution decreased significantly from 164 to 99 l. Absorption was complete and was independent of the dose administered.