Intestinal absorption of aluminium: effect of sodium and calcium

Aluminium (Al) is recognized as a toxin in patients with deficient renal function. Moreover, Al may play a role in some neurodegenerative diseases. It is hypothesized that more than one intestinal absorption mechanism exists for Al, related to various intraluminal chemical species, and that Al shares intestinal transport routes for essential inorganic substances due to similarities in their chemical speciation characteristics. The purpose of the present investigation was to study the ef-fects of ionic Na (0–120 mmol/l) and Ca (0–10 mmol/l), alone and in combination, on the intestinal absorption of ionic Al (20 and 30 mmol/l). A previously standardized method of perfusion of rat small intestine was used, combined with serial blood sampling. Mucosal uptake and systemic appearance of Al in the blood were monitored during 1 h perfusion, together with Na and Ca; the metals were given as the chloride. The intestinal absorption of Na and Ca was taking place according to previously reported mechanisms. A one-sided negative interaction was shown to exist between Ca and Al resp. Al and Na during both mucosal uptake and systemic appearance; Ca interacts negatively with Na during systemic appearance, but enhances mucosal uptake of Na. It may be speculated that Al mimicks Ca in its Na-dependent intestinal passage. Received: 25 February 1997 / Accepted: 1 September 1997     

齐酞酸钠在大鼠肠道吸收动力学研究

目的:研究齐酞酸钠(OAHDPS)在大鼠肠道内的吸收特性.方法:采用大鼠在体小肠吸收实验方法,测定OAHDPS在不同剂量(100,50,25μg·mL-1)下结扎和不结扎胆管条件下的小肠吸收量和吸收速率常数(Ke),并比较各个肠段的吸收.结果:研究表明,OAHDPS在肠道内的吸收机制是被动扩散方式,且在小肠的吸收不受胆汁等分泌物的影响;在肠道正常pH值情况下,平均Ke为(0.162±0.012)h-1;各个肠段对OAHDPS均有吸收且Ke无显著差异.结论:在OAHDPS口服剂型设计时应首先考虑肠溶缓释制剂.     

Intestinal absorption of gabapentin in rats

Gabapentin (1-aminomethyl-)cyclohexaneacetic acid, G? 3450, CI-945; CAS 60142-96-3) is a new gamma-aminobutyric acid (GABA) analogous compound that has shown an anticonvulsive effect as well as low toxicity in preclinical and clinical studies. The substance is well absorbed after oral administration and penetrates the blood-brain barrier. The aim of experiments was to study the mechanism of intestinal absorption, the relationship between the absorption rate and the applied concentration and whether the absorption rate differs between different parts of the intestine. For this purpose, isolated intestinal segments of rats (everted sac preparations) were used. Due to the fact that gabapentin is not metabolized in the intestine, its concentration in the mucosal and serosal compartments could be determined by scintillation counting of 3H-gabapentin. The results showed that gabapentin was absorbed by simple diffusion because neither indications for an uphill nor for a carrier-mediated transport could be demonstrated. The absorption rate was linearly related in the concentration range from 0.001 to 100 mmol/l. There was no significant difference between the absorption rate in the three parts of the small intestine at 1 and 10 mmol/l, while the absorption rate was significantly (p less than 0.01) lower in the colon.     

Effect of triglyceride on small intestinal absorption of cefoxitin in rats

Coadministration of trilaurin or monolaurin with sodium cefoxitin increased its absorption from the small intestine of the rat. Its absorption from the rectum was effected to a lesser extent except when lipase was present. Lipase, a natural constituent of the small intestine fluid, may therefore be essential for the adjuvant action of trilaurin on cefoxitin absorption across the intestinal membrane. Among the triglycerides used, trilaurin and tricaprin were the most effective enhancers of cefoxitin absorption. Both the rate of degradation of triglyceride to its fatty acid component and subsequently the rate of fatty acid absorption were factors influencing the enhancing action. Maintenance of fatty acid concentration at the small intestinal absorption site was shown to be necessary to obtain a cefoxitin bioavailability of up to 70%.     

帕利哌酮大鼠在体肠吸收药物动力学研究

目的:考察帕利哌酮在大鼠各肠段的吸收动力学特征。方法:运用大鼠在体单向灌流技术考察帕利哌酮在大鼠各肠段的吸收动力学特征;采用高效液相色谱法测定灌流液中帕利哌酮的含量;从药物质量浓度、吸收部位、灌流速度、介质pH值4个方面对帕利哌酮的各肠段吸收特性进行考察;利用重量法计算动力学参数。结果:药物的吸收在质量浓度较高时(10.0～20.0μg.mL-1)具有自身抑制现象。灌流速度和介质pH值在考察范围内对药物肠吸收影响显著。考察范围内的药物吸收部位对吸收速率无显著影响。十二指肠、空肠、回肠和结肠的Ka值分别为(6.58±2.35),(7.03±3.33),(7.13±2.77),(3.77±3.42)h-1。结论:帕利哌酮在整个肠道均有吸收,初步推断帕利哌酮在大鼠肠道的吸收机制为主动转运。     

芒果苷大鼠肠吸收特性研究

目的研究芒果苷在大鼠肠道的吸收动力学特征。方法采用大鼠在体肠循环实验,用超高效液相色谱法和紫外分光光度法分别测定芒果苷和酚红的浓度,考察药物浓度、pH值和不同肠段对芒果苷吸收的影响,并与知母水煎液比较芒果苷在大鼠肠道吸收的差异。结果芒果苷浓度为2.0,5.0,10.0,20.0μg.mL-1时,吸收速率常数(ka)分别是0.0541,0.0467,0.0491,0.0220 h-1,吸收百分率(Fa)分别是14.05%,13.14%,12.43%和5.82%;随肠液pH升高,ka和Fa依次增加;芒果苷在肠段内吸收存在差异,各肠段的吸收速率常数按结肠、十二指肠、回肠和空肠依次下降;知母水煎液组中,肠循环液中芒果苷含量的上升和新芒果苷含量的下降呈同步变化。结论芒果苷在大鼠小肠段的吸收存在高浓度饱和现象,并且受到药物浓度、肠循环液pH值、肠段等因素的影响。     

Intestinal absorption of cefixime in rats 1

目的：研究头孢克肟（Ｃｅｆ）的肠吸收特性及影响Ｃｅｆ吸收的因素．方法：采用一种改良的在体肠回流技术,对Ｃｅｆ从肠内消失速率进行研究．用反相高压液相色谱法对回流液中Ｃｅｆ浓度进行分析．结果：Ｃｅｆ主要从小肠的上部吸收,从肠中的消失速率有明显的ｐＨ依赖性．Ｃｅｆ在００１－０５ｍｍｏｌ·Ｌ－１范围内的吸收速率为一曲线．依地酸钠能够明显促进Ｃｅｆ的肠内消失速率．结论：Ｃｅｆ部分是经载体转运的,且又具有明显的细胞外转运特征     

辛伐他汀在大鼠中在体肠吸收动力学研究

目的：研究辛伐他汀在大鼠各肠段的吸收动力学。方法：采用大鼠在体肠段灌流实验，以HPLC法测定辛伐他汀和酚红在肠回流液中的浓度，观察吸收部位、药物浓度、pH值3个因素对辛伐他汀肠吸收特性的影响。结果：辛伐他汀在大鼠肠道内无特定吸收部位，在十二指肠、结肠、空肠和回肠的吸收速率常数分别为0．0397、0．0342、0．0316、0．0282／h。在pH5．0～7．4范围内药物吸收不受pH值影响。结论：辛伐他汀在大鼠全肠段均有吸收，符合一级动力学特征，吸收机制为被动扩散，适于制备日服1次的缓释给药系统。     

阿克他利大鼠在体肠吸收动力学

目的研究阿克他利大鼠在体肠吸收动力学特征。方法采用大鼠在体单向灌流法进行肠吸收实验,以吸收速率常数(ka)和表观吸收系数(Papp)为指标,从灌流速度、药物浓度和吸收部位3个方面对阿克他利肠吸收动力学特征进行考察。结果不同灌流速度下的ka和Papp有极其显著性差异(P<0.01);药物浓度在一定范围内对ka和Papp无显著性影响(P>0.05);小肠各段(十二指肠、空肠、回肠)的ka和Papp无显著性差异(P>0.05);小肠与结肠的ka存在极其显著性差异(P<0.01),Papp存在显著性差异(P<0.05)。结论阿克他利在整个肠道吸收良好,但吸收窗主要在小肠,在结肠段的吸收相对较差。     

依托度酸大鼠在体肠吸收动力学

目的考察依托度酸在大鼠各肠段的吸收动力学特征。方法运用大鼠在体单向灌流技术考察依托度酸在大鼠各肠段的吸收动力学特征;采用高效液相色谱法(HPLC)测定灌流液中依托度酸的含量;从药物质量浓度、吸收部位、灌流速度、pH值4个方面对依托度酸的各肠段吸收特性进行考察;利用重量法计算动力学参数。结果灌流速度和一定范围内的pH值(5.4～7.4)对药物吸收速率常数(ka)和表观吸收系数(Papp)影响显著;一定范围内的药物浓度对ka和Papp无显著影响;十二指肠、空肠、回肠和结肠的ka值分别为(0.082 7±0.003 8)、(0.077 5±0.004 5)、(0.073 3±0.006 4)、(0.064±0.009 3)min-1。结论依托度酸在大鼠肠道的吸收呈现一级动力学特征,且吸收机制为被动扩散。依托度酸在整个肠道均有吸收。     

头孢克肟在大鼠肠内的吸收

AIM: To study the intestinal absorption characters of cefixime (Cef) and the factors affecting Cef absorption. METHODS: A rat intestine loop in situ technique was used to investigate the disappearance rate of Cef from the intestine. Cef concentration in the flux was measured by the reversed phase HPLC. RESULTS: Cef was mainly absorbed from the upper part of the intestine. Its disappearance rate was apparently pH-dependent [(5.8 +/- 0.6) nmol.h-1/(g wet tissue) at pH 7.4, (8.9 +/- 1.4) nmol.h-1/(g wet tissue) at pH 5.0, P < 0.05)]. The uptake rate of Cef was curvilinear at 0.01-0.5 mmol.L-1. The values of apparent Kt, Jmax, and Kd were 0.114 mmol, 78.41 nmol.h-1/(g wet tissue), and 43.70 nmol.h-1.mmol-1/(g wet tissue), respectively. Sodium edetate markedly promoted the disappearance rate of Cef from the intestine. CONCLUSION: Cef was transported partly via carrier-mediated transport system and partly via the paracellular transport system.     

Intestinal absorption characteristics of ketoprofen in rats

The present study aims to investigate the intestinal absorption characteristics of ketoprofen in rats. The pharmacokinetic profile of ketoprofen was evaluated following a single p.o. administration of ketoprofen (1 mg/kg) to rats in the absence and presence of benzoic acid or lactic acid (2 and 10 mg/kg), the substrates of monocarboxylic acid transporters. The pharmacokinetic profiles of ketoprofen (1 mg/kg) were significantly altered by the concurrent use of benzoic acid or lactic acid (10 mg/kg), compared with the control (given ketoprofen alone). The Cmax and AUC of ketoprofen in the presence of benzoic acid or lactic acid (10 mg/kg) were significantly (p<0.05) lower than those from the control group, while there was no significant change in Tmax and the terminal plasma half-life (T1/2) of ketoprofen. These results suggest that ketoprofen shares a common transport pathway with benzoic acid and lactic acid during the intestinal absorption in rats.     

牡荆素鼠李糖苷的大鼠在体肠吸收动力学

目的 研究牡荆素鼠李糖苷(RHV)的大鼠在体肠吸收动力学特征.方法 采用HPLC法测定RHV在肠循环液中的药物浓度;采用UV法测定肠循环液中酚红浓度;以大鼠原位灌注模型考查RHV的肠吸收动力学情况.结果 RHV 浓度为20、10、5μg·ml-1的吸收速率常数(Ka)分别为0.0416、0.0478、0.0312 h-1;肠循环液pH4、6、8时RHV的Ka分别为0.0253、0.0478、0.0588 h-1;RHV在十二指肠、空肠、回肠和结肠时的Ka分别为0.0479、0.0308、0.0322、0.0305 h-1.结论 RHV 浓度对RHV的Ka无显著性影响;在pH4～8时,随肠循环液pH的增大,RHV的Ka增加;RHV在大鼠十二指肠、空肠、回肠和结肠的吸收无显著性差异(P＞0.05);RHV在大鼠肠道的吸收呈一级动力学过程,吸收机制为被动扩散.     

甲硝唑大鼠肠吸收实验研究

目的考察甲硝唑在大鼠不同肠段的吸收动力学特征、吸收部位及吸收机制,为其结肠定位缓控释制剂的设计提供理论依据。方法采用大鼠在体灌流肠吸收实验,考察了甲硝唑的吸收部位和吸收动力学特征。结果甲硝唑在大鼠肠道内无特定吸收部位,各肠段吸收速率常数按十二指肠、空肠、结肠、回肠顺序依次上升,吸收速率常数分别为0.078、0.136、0.155、0.168/h。在2～20μg/ml的浓度范围内,甲硝唑的吸收量与浓度有良好的线性关系。结论甲硝唑在大鼠全肠段均有吸收,吸收符合一级动力学特征,吸收机制为被动扩散,适于制备结肠定位缓控释制剂。     

Rate-controlled rectal absorption enhancement of cefoxitin by co-administration of sodium salicylate or sodium octanoate in healthy volunteers.

1. The effects of sodium octanoate and sodium salicylate on the rectal absorption of cefoxitin were investigated in healthy volunteers. Drug solutions were given either as a bolus or as a zero-order infusion. 2. On rectal infusion sodium octanoate and sodium salicylate both enhanced mean cefoxitin bioavailability (+/- s.d.) from 5.0 +/- 1.2% to 9.1 +/- 1.3% and 9.2 +/- 1.5%, respectively. After rectal bolus delivery octanoate increased the mean cefoxitin bioavailability from 7 +/- 3% to 17 +/- 3%, whereas bolus salicylate did not produce a statistically significant effect. All formulations were well tolerated by the volunteers. 3. It is concluded that both octanoate and salicylate are capable of enhancing rectal cefoxitin absorption in man; rate of delivery seems to be an important factor.     

田蓟苷微乳在大鼠小肠吸收特性的研究

<正>香青兰(Dracocephalum moldevica L.)为唇形科青兰属植物,具有治疗高血压、高血脂、心绞痛和冠心病作用,田蓟苷(Tilianin)是其主要活性成分[1-2]。因其水溶性差,口服给药吸收不理想[3]。为增加田蓟苷溶解度,课题组前期进行了微乳制备工艺的研究[4]。在此基础上,依据大鼠与人小肠生理状况相似的特点[5],采用大鼠在体单向灌流模型和外翻肠囊模型考察田蓟苷肠灌流液、田蓟苷微乳在大鼠各肠段吸收     

Intestinal absorption and excretion of aflatoxin in rats

Aflatoxin B1 (AFB1) transfer across the gastrointestinal tract was studied in rats. The rate of biliary secretion of 3H was higher when [3H]AFB1 was injected into the small intestine than when injected into the stomach. When various sites of the small intestine were perfused with the medium containing [3H]AFB1, the highest rate of disappearance of 3H from the medium was noted in the duodenum. Also the rate of biliary secretion of 3H tended to be higher when the duodenum was perfused than when the other sites were perfused. These results suggest that AFB1 is absorbed mainly from the small intestine, most efficiently from the duodenum. Uptake of AFB1 by the everted intestine in vitro was slightly greater in the jejunum than the other sites, suggesting that the cause of the differences in the intestinal absorption among various sites may reside in the transfer process of AFB1 from the epithelial cell layer to vascular circulation. Comparison of the AFB1 appearance in the mesenteric venous plasma and lymph showed that AFB1 is absorbed almost exclusively in the vein. Distribution of 3H in the mesenteric plasma on thin-layer chromatography revealed that metabolic degradation of AFB1 takes place in the duodenal and jejunal tissues during the course of AFB1 absorption. Examination of the appearance of AFB1 or 3H in the intestinal perfusate after iv injection of of AFB1 or [3H]AFB1 suggested that AFB1 and its metabolites can transfer from the blood to the intestinal lumen. The rate of the AFB1 absorption from various sites of the intestine changed with age and reproductive stage, indicating that the AFB1 transfer across the intestinal wall is under the influence of the growth and reproductive endocrine condition.     

The synergistic effects of concurrent administration to rats of EDTA and sodium salicylate on the rectal absorption of sodium cefoxitin and the effects of inhibitors

Plasma levels of cefoxitin, as enhanced by rectal coadministration of sodium salicylate, were reduced by concurrent administration of less than 0.5 mg mL-1 N-ethylmaleimide (NEM) or p-chloromercuriphenylsulphonic acid, sodium salt (p-CMP). Concentrations of these inhibitors above 1 mg mL-1 resulted in enhanced peak plasma values of cefoxitin. This did not occur after coadministration with either ethylenediaminetetraacetic acid (EDTA) or polyoxyethylene-23 lauryl ether (POE). Ouabain and 2,4-dinitrophenol (DNP) suppressed plasma cefoxitin levels in the presence of salicylate and the enhancing effects of EDTA and POE when EDTA and POE were administered at low doses. At higher concentrations of EDTA and POE, DNP had little effect, while ouabain had little effect on POE and only partially suppressed the effects of EDTA. Plasma concentrations of cefoxitin after coadministration with salicylate and POE together, or with EDTA and POE together, were about the same as expected from summing the plasma levels resulting from coadministration of each adjuvant individually at the same concentrations. However, combined administration of salicylate and EDTA with cefoxitin yielded plasma cefoxitin concentrations which were much higher than expected from the sum of their individual actions.     

芒果苷大鼠在体肠吸收动力学研究

目的研究芒果苷在大鼠小肠内的吸收情况及动力学特征。方法采用大鼠在体单向灌流法进行肠吸收实验,利用HPLC法测定灌流流出液中芒果苷的浓度,按重量法计算动力学参数。结果芒果苷在小肠内吸收存在差异,在十二指肠、空肠、回肠和结肠的Ka分别为（1.4±0.1）、（1.6±0.2）、（0.9±0.1）、（1.0±0.2）×10-2.min-1;与0.32mg.L-1浓度相比,7.0mg.L-1浓度的Ka和Papp值显著降低。结论芒果苷在小肠内吸收存在高浓度饱和现象,且存在特定的吸收部位,主要在十二指肠和空肠。