普拉克索的大鼠在体肠吸收

采用大鼠在体灌流法,以灌流液中剩余药物浓度为指标,考察普拉克索(1)在不同吸收部位的吸收动力学特征以及不同pH、不同药物浓度对1全肠段吸收的影响.结果显示,1在不同肠段的吸收速率常数(h-1)分别为:十二指肠0.295、结肠0.513、回肠0.480 h和空肠0.808 h.药物在大鼠全肠道内的吸收量随药物浓度的增大而升高,药物浓度和pH对吸收速率常数无显著性影响.1在肠道的吸收符合一级动力学特征,吸收机制为被动吸收.采用大鼠在体胃灌注法,以胃灌注液中药物前后浓度变化计算1在胃部吸收情况.结果表明1几乎不吸收.     

肠吸收促进剂的研究进展

肠吸收促进剂可改善肠粘膜透过能力低药物的口服生物利用度。本文综述了肠吸收促进剂研究的实验方法、制剂及生理因素对其促吸收作用的影响、安全性问题以及近年重点研究的促进剂类型。     

替米沙坦的大鼠肠吸收特性及联用药物对其吸收的影响

目的:研究替米沙坦在大鼠肠道的吸收情况及联用药物对其吸收的影响。方法:采用大鼠在体单向灌流法进行肠吸收实验,研究药物浓度、肠段及联用药物硝苯地平、尼莫地平、氨氯地平、卡维地洛和胺碘酮对替米沙坦肠吸收的影响。结果:替米沙坦在十二指肠、空肠、回肠、结肠段的吸收速率常数(Ka)和表观吸收系数(Papp)均无显著性统计学差异(P>0.05)。随着浓度的增高,替米沙坦的Ka和Papp值显著性增大。乙胺碘呋酮和硝苯地平对替米沙坦在空肠段的Papp和Ka存在显著性影响(P<0.05);但卡维地洛、尼莫地平和氨氯地平未见显著性影响(P>0.05)。结论:替米沙坦肠吸收机制可能以被动扩散为主,其转运过程可能受P-gp等外排泵的影响,且在全肠道吸收良好,无特定吸收部位。合并用药可能影响替米沙坦的肠吸收。     

苯丙醇胺肠吸收特性的研究

目的;研究苯丙醇胺在肠道中的吸收特点。方法：采用在体大鼠肠段回流实验,对苯丙脑胺的吸收特性从其主要影响因素ＰＨ值,吸收部位,药物浓度３个方面进行研究。结果：回流液的ＰＨ值对吸收有显著影响,ＰＨ值在７．４－６．５之间呈特定吸收;在十二指肠及空肠上,中段的吸收明显大于下段和回肠,药物浓度在５０－４００μｇ．ｍｌ＾－１范围内无高浓度饱和现象,吸收系数基本保持不变。     

穗花杉双黄酮大鼠在体肠吸收动力学的研究

采用大鼠在体单向肠灌流实验模型,用HPLC-UV法测定灌流液中药物浓度,研究穗花杉双黄酮肠吸收动力学。结果表明穗花杉双黄酮在十二指肠、空肠、回肠和结肠的吸收速率常数（Ka）、药物表观渗透系数（Papp）差异无统计学意义（P>0.05）,提高药物浓度的吸收速率常数基本保持不变。在大鼠各肠段均有吸收,无特定吸收部位,吸收机制为被动扩散。     

法莫替丁大鼠在体小肠吸收动力学研究

应用大鼠在体肠吸收实验方法研究了法莫替丁各肠段的吸收动力学特征。实验表明 :法莫替丁在肠道各部位的吸收速率按十二指肠、空肠、回肠、结肠顺序下降 ,吸收速率常数分别为0 0 5 0 8,0 0 44 6 ,0 0 415 ,0 0 2 87h-1。药物在肠道内的吸收呈现一级吸收动力学过程 ,其吸收机制为被动扩散     

左卡尼汀大鼠体内肠吸收动力学的研究

目的考察左卡尼汀在大鼠各肠段的吸收动力学特征。方法应用大鼠在体肠回流试验装置,应用UV法和HPLC法,分别测定肠循环液中酚红和左卡尼汀的量。结果左卡尼汀在药物浓度为0.5、1、2 mg/mL时,全小肠段的吸收速率常数分别为0.187 4、0.179 8、0.174 2/h;不同pH值(7.9、6.5、4.8)时的吸收速率常数分别为0.179 8、0.325 9、0.484 9/h;在十二指肠、空肠、回肠的吸收速率常数分别为0.180 5、0.209 8、0.209 7/h。结论不同的药物浓度、不同肠段对药物在肠道的吸收无显著影响;随着pH值的减小,左卡尼汀的Ka值显著增大;药物的吸收呈一级动力学过程,吸收机制为被动扩散。     

药物肠道吸收研究方法

药物在肠道内的吸收程度和吸收特征是影响口服药物生物利用度的重要因素。肠道吸收研究可以预测影响药物在肠道吸收的机制与因素,研究方法主要包括体内法（invivo）、在体法（insitu）、体外法（invitro）等。就目前药物小肠吸收的研究方法及其特点进行综述。     

硫酸沙丁胺醇大鼠在体肠吸动力学研究

目的研究硫酸沙丁胺醇在大鼠各肠段的吸收动力学特征。方法采用大鼠在体肠回流法进行动力学试验,从吸收部位、药物浓度、pH值等方面对药物在体内的各个肠段的吸收特性进行研究。结果硫酸沙丁胺醇在大鼠肠道中的吸收不受药物浓度、回流介质pH值等的影响,在分肠段试验中,吸收速率常数Ka(1/h)依次为十二指肠0.052,空肠0.046,回肠0.042,结肠0.030,结肠的吸收显著低于十二指肠、空肠和回肠段;在pH5.4~7.8回流介质中吸收无显著差异,在50~200μg/mL浓度范围内,药物吸收量与浓度呈线性关系。结论硫酸沙丁胺醇在大鼠体内各肠段均有吸收,吸收机制以被动扩散为主,适于制成Tlag<5 h的口服迟释制剂。     

天山雪莲提取物主要成分的大鼠在体肠吸收动力学

目的:研究天山雪莲主要活性成分绿原酸和芦丁的大鼠在体肠吸收动力学。方法:采用单向灌流实验技术,利用HPLC法测定绿原酸和芦丁的量,分别研究药物质量浓度及吸收部位对绿原酸和芦丁吸收的影响。结果:药物质量浓度对绿原酸和芦丁吸收速率常数(Ka)和表观吸收系数(Papp)无显著性影响;绿原酸和芦丁在小肠各段间吸收的Ka和Papp无显著性差异,但与结肠相比吸收明显增大。结论:一定范围的药物浓度对绿原酸和芦丁的Ka和Papp无显著性影响,其吸收机制为被动扩散。药物在全肠道吸收较好,吸收窗主要在小肠,且小肠内无明显的特定吸收部位。     

Influence of intestinal efflux pumps on the absorption and transport of furosemide

Purpose

Furosemide is a commonly used diuretic which is used in the treatment of edema, congestive heart failure, hypertension and renal failure. Its absorption exhibits inter- and intra-subject variability that can be attributed to many factors including the intestinal efflux pumps such as the P-glycoprotein (P-gp). This study was done due to the great disagreement between what is published in the literature regarding the influence of P-gp on furosemide and at the same time due to the importance of this drug in the treatment of different conditions as described above. In addition, an investigation of the effect of two of the commonly used pharmaceutical excipients (hydroxypropyl β-cyclodextrin [HPβCD] and Tween 80) and also a P-gp inhibitor (verapamil hydrochloride) on the intestinal absorption of this drug were also done.

Methods

The study utilized the everted intestinal sacs technique to investigate both the effect of the efflux transporter (P-gp) on furosemide absorption and also the effect of the chosen excipients.

Results

The absorption of furosemide was significantly influenced by the P-gp as confirmed by the everted vis the non-everted sacs together with the verapamil study in which the transport of furosemide was inhibited by verapamil. In addition, Tween 80 was also shown to inhibit the P-gp pump whereas the HPβCD did not significantly influence the efflux of furosemide in this study.

Conclusions

P-glycoprotein and some of the used excipients in the formulation play a very important role in the transport of furosemide and other drugs. Thus excipients that affect the activity of P-gp should be avoided when formulating drugs that are substrate for the P-gp or other efflux pumps.     

ABC跨膜转运蛋白外排抑制剂促进药物肠吸收的研究进展

药物的肠吸收受肠道内的外排转运蛋白影响,其中ABC跨膜转运蛋白为目前已知的主要外排转运蛋白。近年开发的可直接抑制转运蛋白外排作用的外排抑制剂大多属于非离子表面活性剂和植物天然成分。本文综述这两类外排抑制剂的研究进展。     

5‐Fluorouracil treatment alters the expression of intestinal transporters in rats

5‐Fluorouracil (5‐FU), an anticancer drug, causes severe gastrointestinal damage, which may affect the absorption of orally administered drugs including the substrates of intestinal uptake and efflux transporters. This study aimed to investigate quantitatively the effect of 5‐FU‐induced intestinal damage on the expression of intestinal transporters: P‐glycoprotein (P‐gp), breast cancer resistance protein (BCRP) and peptide transporter 1 (PEPT1) in rats. The rats were treated with 5‐FU (30 mg/kg/day, p.o. ) for 5 days to induce intestinal damage, and then the upper, middle and lower intestinal segments were removed. The mRNA and protein expression levels of these transporters in each segment were determined using quantitative real‐time PCR and Western blotting, respectively. In the 5‐FU‐treated rats, the protein levels of P‐gp and Bcrp in the upper segment were significantly increased to 15‐ and 2.6‐fold of the control, respectively, while those in other segments were unaffected. Pept1 expression was increased by 5‐FU in almost all segments. A remarkable increase in P‐gp expression was shown, the uptake of digoxin, a P‐gp substrate, in each intestinal segment was measured using a rat everted sac. As a result, the uptake of digoxin in the upper segments of 5‐FU‐treated rats was decreased compared with that of the control. In conclusion, 5‐FU‐induced intestinal damage was shown to alter the expression of these transporters, especially in the upper intestinal segment, while the characteristics of the influence varied among the transporters. The 5‐FU‐induced intestinal damage may affect transporter‐mediated drug absorption of orally administered drugs in the clinical setting.     

Effect of Methotrexate on Drug Absorption from the Rat Small Intestine in Situ and in Vitro

Abstract The effect of methotrexate (20 mg/kg intramuscularly) on the absorption of phenobarbitone, sulphafurazole, mecamylamine, quinidine and isoniazid from the rat small intestine was studied in situ and in vitro. The disappearance of all drugs studied from the intestinal fluid in situ was retarded on the third day after methotrexate administration. The fluid transfer and the amount of drugs passed through the intestinal wall in vitro were also decreased. The absorption of phenobarbitone was reversible within six days, whereas the absorption of quinidine was still retarded on the sixth day after methotrexate administration. Methotrexate did not modify the amount of quinidine excreted into the intestinal lumen after intravenous administration. The levels of other drugs except isoniazid in the blood at the end of the experiment showed changes corresponding to their disappearance from the intestinal lumen. In situ the drug levels in the intestinal wall were much lower than in vitro. Their levels in the intestinal wall reflected drug absorption in vitro but not in situ. The methotrexate-induced reversible decrease in absorption seems to be attributable at least partly to diminished water flux through the intestinal wall, although other mechanisms may also exist.     

药物肠道吸收机制中转运载体、酶、电位的研究进展

口服药物的肠道吸收是一个复杂的过程，既取决于药物本身的理化特性，又取决于机体的因素及吸收环境。本文从转运载体、酶、电位等几个方面综述了近年来药物肠道吸收机制的研究概况。     

药物肠道吸收研究方法概述

口服药物肠道吸收的研究方法主要包括体外法、体内法和在体法，对这3种研究方法进行简要介绍。鉴于在体肠灌流法操作简便、技术成熟、可控性强，同时又保证了神经内分泌调节与淋巴液血液供应的完整性等特点，更能反映药物吸收的真实情况，因此重点介绍了在体肠灌流法，并对在体肠灌流法中使用的循环灌流法和单向灌流法常用的几种灌流液体积校正方法等进行综述，为研究口服药物肠道吸收试验设计提供借鉴和参考。为保证试验的可操作性和实验结果的准确性，认为应根据所研究药品的性质、实验要求、试验条件等多方面因素综合考虑，选择适宜的试验方法，进而为药物剂型的开发和临床合理用药提供依据。     

Drug Absorption from the Small Intestine of the Triparanol–Treated Rat in Situ

Abstract The effect of treatment with triparanol (25 mg/kg by gavage every 24 hours for three weeks) on the absorption of phenobarbitone, sulphafurazole, isoniazid, mecamylamine and quinidine from the rat small intestine was studied in situ by measuring their disappearance from the intestinal lumen. The appearance of sulphafurazole and mecamylamine in the intestinal lumen was also studied after their intravenous administration, and the partitioning of mecamylamine between the buffer solution and the intestinal tissue was measured in vitro. Treatment with triparanol retarded the absorption of sulphafurazole, whereas the absorption of mecamylamine was accelerated. The amount of sulphafurazole and mecamylamine in the intestinal lumen after their intravenous administration was relatively slight. The in vitro partitioning of mecamylamine into the intestinal tissue was higher in triparanol–treated than in control intestines. Triparanol did not change the absorption of phenobarbitone, isoniazid or quinidine. Phenobarbitone in the whole blood at the end of the experiment was increased after triparanol, but the levels of other drugs were unchanged. Triparanol did not modify drug concentrations in the intestinal wall at the end of the experiment. The relatively slight changes in drug absorption induced by triparanol are probably due to changes in the morphology and composition of the intestinal wall.     

Effect of Colchicine on Drug Absorption from the Rat Small Intestine in Situ and in Vitro

Abstract The effect of colchicine (1 mg/kg intraperitoneally on two successive days) on the absorption of isoniazid, quinidine and sulphafurazole (sulfisoxazole) from the rat small intestine was studied in situ and in vitro. Colchicine produced two different types of histological damage in the small intestine, one with degenerative and the other with regenerative changes predominating. The small intestinal surface area was variably reduced. The colchicine-treated rats were lethargic and hypothermic as compared to controls. Colchicine retarded the disappearance of fluid and all three drugs from the small intestinal lumen in situ 2 days after the first colchicine injection. In vitro the total amounts of fluid and drugs passed through the intestinal wall were not significantly changed by colchicine, although there was a slight tendency towards an increased absorption of quinidine. Hence, colchicine as an antimitotic drug decreases drug absorption from the rat small intestine in situ, apparently due to the decreased surface area of the small intestine, the decreased water flux through the intestinal wall, the retarded intestinal motility and hypothermia of the rats. In vitro the changes are small, which makes the in vitro tests less suitable for studying the effect of colchicine on absorption.     

药物肠道吸收研究方法

药物在肠道内的吸收程度和吸收特征是影响口服药物生物利用度的重要因素。肠道吸收研究可以预测影响药物在肠道吸收的机制与因素,研究方法主要包括体内法（in vivo）、在体法（in situ）、体外法（in vitro）等。就目前药物小肠吸收的研究方法及其特点进行综述。