外翻肠囊法研究姜黄素促进葫芦素B肠段吸收作用

目的:建立大鼠肠吸收模型,考察对葫芦素B的吸收以及姜黄素对葫芦素B吸收的促进作用。方法:采用大鼠离体外翻肠囊模型,通过HPLC法测定肠囊内样品溶液中葫芦素B的含量,研究葫芦素B在不同肠段的吸收特性和不同比例姜黄素对葫芦素B的促吸收作用。结果:葫芦素B的肠吸收随其浓度的升高而增大,当葫芦素B联合不同比例姜黄素后,百分吸收率(P%)、累计吸收量(Q)和吸收速率常数K_a值均具有显著性差异。结论:葫芦素B主要吸收部位为十二指肠,且在大鼠肠内主要以被动扩散方式吸收;姜黄素能够促进葫芦素B的大鼠肠吸收,且呈浓度依赖性。     

The effects of PLGA microparticles on intestinal absorption of p-glycoprotein substrate using the everted rat intestinal sac model

In addition to the effects of physical processes (solubility, tissue permeability, and formulation factors), p-glycoprotein (P-gp) efflux across the apical membrane of enterocytes can affect the rate and amount of compound diffusing across the basolateral membrane of the intestine and entering the blood stream. The first objective was the evaluation of a possible role of intestinal P-gp in the kinetic absorption of a model drug: furosemide. To achieve this goal, two series of transport experiments, apical to basolateral (A → B) and basolateral to apical (B → A) with and without verapamil -a known P-gp inhibitor- were performed. The second objective was to evaluate whether encapsulation into polymeric microparticles might improve the oral absorption of a poorly permeable drug. Thus, spherical poly lactic-glycolic acid (PLGA) microparticles of furosemide were designed, and the concentration of transported drug was evaluated using an in situ everted rat gut sac model. The results indicated that verapamil at various drug concentrations (5–100 μg/mL) significantly decreased the B → A (2–3 fold) and increased the A → B (1.5–2 fold) permeability of furosemide, which showed that this drug could be a P-gp substrate. We found that encapsulation of furosemide in PLGA microparticles can markedly increase (2–4 fold) intestinal absorption of drug even higher than verapamil does. We conclude that biodegradable microparticles are a promising strategy to increase the bioavailability of drugs and have advantages compared to P-gp inhibitors with pharmacological and severe side effects at doses required for efflux pump inhibition.     

The intestinal permeation of didanosine from granules containing microspheres using the everted gut sac model

The aim of this research is to evaluate the intestinal permeation of a new formulation (NF) for the anti-retroviral didanosine (ddI) drug, using the everted gut sac model. The NF is composed by granules containing ddI incorporated in chitosan microspheres, plus free chitosan as an excipient. The permeation was evaluated across the three intestinal segments of adult male Wistar rats. The performance of ddI permeation from the NF was compared to the same granules without free chitosan and to buffered ddI tablets as control. The permeations across duodenum were higher than across jejune and ileum. The ddI from NF presented higher permeation and a crescent-shaped profile in duodenum compared to the other formulations. Such effects are provided by the superior mucoadhesiveness to the intestinal membrane and potentialize sustained release properties for NF. These results lead one to consider the novel formulation to be promising for ddI administration by oral route.     

Excipients enhance intestinal absorption of ganciclovir by P-gp inhibition: assessed in vitro by everted gut sac and in situ by improved intestinal perfusion

In rats we examined the effects of some common excipients on the intestinal absorption of ganciclovir (GCV), a BCS-III drug and substrate of P-gp, by assessing its in vitro transfer from mucosa to serosa and in situ transepithelial permeation. In vitro, all selected excipients (concentration range 0.1-1% [w/v]) could increase the transport amount of GCV in the everted gut sac model. Whereas enhancement by F-68 demonstrated regional differences like verapamil, PEG-400, Tween-80 and EL-35 exhibited no regional differences. In situ studies were performed by an improved perfusion model, single-pass perfusion with whole small intestine, to determine more accurately the permeability of lipophobic compounds. The permeability of GCV was significantly increased by all excipients. The effects of EL-35 and F-68 were dose-dependent but those of PEG-400 and Tween-80 were not. The results suggest that enhancements of intestinal absorption of GCV by these excipients are probably due to inhibition of P-gp-mediated drug efflux. It could be deduced from their different properties that both blocking binding sites of P-gp and altering membrane fluidity were involved in their P-gp-inhibition. The former mechanism might be involved for F-68, while the latter one might account for the effects of PEG-400, Tween-80 and EL-35.     

Evidence of efflux-mediated and saturable absorption of rifampicin in rat intestine using the ligated loop and everted gut sac techniques

This study was carried out to explore whether efflux-mediated and saturable mechanisms play any role toward poor and variable intestinal absorption of rifampicin. In situ segmental permeability of rifampicin at various residence times was determined in rat gastrointestinal tract using the ligated loop technique. The involvement of efflux-mediated and saturable absorption of rifampicin was studied in rat intestine using the everted sac method. The samples were analyzed by a validated HPLC method. Rifampicin showed decreased permeability in jejunum and ileum with an increase in residence time. The permeation of rifampicin from the serosal to the mucosal side (secretion) was significantly higher than permeation from the mucosal to the serosal side (absorption) of jejunum and ileum. This indicated the involvement of efflux-mediated transport. Addition of verapamil, an inhibitor for P-glycoprotein (Pgp), multidrug resistance associated protein-2 (MRP-2), and other related transporters, increased absorption of rifampicin in jejunum and ileum by 2-3-fold and decreased secretion by almost 4-fold. The permeation rate (flux) of rifampicin through duodenum increased with concentration up to 300 microg/mL, becoming constant thereafter, indicating the existence of saturable absorption. There was no saturable permeation in jejunum and ileum. Thus the present study indicates the involvement of efflux-mediated and saturable absorption mechanisms of rifampicin in rat intestine, which act as barriers to the absorption of the drug. This explains the drug's poor absolute bioavailability. As Pgp varies from person to person to an extent of 2-8-fold, it can be one direct reason for the interindividual variable bioavailability shown by rifampicin.     

大鼠离体外翻肠囊模型对豆腐果苷分肠段吸收初步研究

目的:基于大鼠离体外翻肠囊模型探讨豆腐果苷在不同肠段的吸收情况。方法:建立豆腐果苷及其代谢产物高效液相色谱同时检测方法。在不同肠段(十二指肠、空肠、回肠、结肠)的外翻肠囊模型中加入含豆腐果苷的Krebs-Ringer液,不同时间点(5,10,15,30,45,60,75,90 min)取样并测定囊内药物浓度,比较四个肠段对豆腐果苷的吸收情况。结果:所建立的高效液相色谱法成功应用于豆腐果苷及其代谢产物同时检测。豆腐果苷及其代谢产物吸收迅速并呈明显的时间依赖性,十二指肠段的吸收与代谢情况均高于其他肠段。结论:十二指肠肠段是豆腐果苷分肠段吸收与代谢的主要部位,这是豆腐果苷肠段代谢研究的首次报道。     

HPLC-MS analysis of Schisandra lignans and their metabolites in Caco-2 cell monolayer and rat everted gut sac models and in rat plasma

The absorption profiles of Schisandra chinensis were evaluated using the human Caco-2 cell monolayer and rat everted gut sac models, as well as in rat plasma. By analyzing the chromatographic and MSⁿ characteristics of individual peak acquired by HPLC-DAD-APCI-MSⁿ determination, thirteen lignans were identified as the major in vitro absorbable components of the Schisandra extract. Most of these compounds were also detected and identified in rat plasma after an oral administration of the Schisandra extract, except for angeloyl(tigloyl)gomisin H and angeloyl(tigloyl)gomisin Q, whose structures possess an ester group at the cyclooctadiene ring. In addition, four metabolites, corresponding to the hydroxylation and demethylation products of schisandrin and the hydrolysis derivative of angeloyl(tigloyl)gomisin Q, were tentatively identified. The results demonstrate that Schisandra lignans are the major absorbable components of this crude drug, and hydroxylation, demethylation and hydrolysis are important metabolic transformations of the absorbable lignans.     

Comparative mucoretention of sucralfate suspensions in an everted rat esophagus model.

A simple, rapid, and reproducible in vitro model was established to quantify the relative esophageal mucoadhesive properties of viscous liquid formulations, and the model was applied to compare marketed sucralfate suspensions (Gastrogel, Antepsin, and Ulcogant) to better understand differences in clinical performance. Rat esophageal mucosal segments were everted onto a glass rod and briefly immersed into a liquid formulation containing 51Cr microspheres. Indirect quantification of the retained formulation provided excellent recovery (98.7-101%) and reasonable precision (1.06-38.3% CV). Mucosal retention profiles of the formulations were determined by rinsing the coated tissue in relevant gastrointestinal fluids using the technique of reciprocating vertical immersion. Dispersions of the mucoadhesive hydrogel Carbopol 934P were employed to initially characterize the performance of the model with respect to composition of the rinse fluids, and type and amount of shear force during rinsing. Retention of Carbopol was sensitive to the mechanics of rinsing and to salivary salts but not mucin in the rinse medium. A sucralfate gel suspension (Gastrogel) showed much greater mucoadhesion and resistance to removal by saliva than two non-gel suspensions (Antepsin, Ulcogant). Results suggest that in situ gelation may be a contributing mechanism for strong esophageal retention. These in vitro results are in general agreement with published human esophageal retention data on similar sucralfate suspensions and lend credence to the everted rat esophagus as a qualitatively predictive in vitro model for development of esophageal mucoadhesive liquids.     

广枣提取物大鼠肠外翻的吸收研究

目的研究广枣提取物中2种主要代表性成分没食子酸和原儿茶酸在大鼠不同肠段、不同时间的吸收规律。方法构建大鼠肠外翻模型,应用HPLC法测定广枣提取物肠吸收液中没食子酸和原儿茶酸含量,计算其吸收参数,并分析其在大鼠小肠不同部位、不同时间的吸收特征。结果 2.5h为肠外翻最终检测时间点,在建立的分析色谱条件下,没食子酸和原儿茶酸色谱峰处台氏液和广枣提取物中其他成分对其无干扰,专属性良好。广枣提取物中原儿茶酸和没食子酸在各肠段均为线性吸收,r2值均达到0.90以上,不同肠道部位的累计吸收结果为:十二指肠>空肠>回肠>结肠。结论广枣提取物中原儿茶酸和没食子酸在肠道的吸收特征符合零级吸收速率,其最佳吸收部位为十二指肠。     

UPLC快速测定葛根芩连汤肠外翻囊样品中6个黄酮类成分含量

目的:建立UPLC法同时测定葛根芩连汤肠外翻囊样品中6个黄酮类成分(葛根素、大豆苷、甘草苷、野黄芩苷、黄芩苷、汉黄芩苷)的含量。方法:样品用甲醇提取,采用Agilent Proshell 120 EC-C18(4.6 mm×50 mm,2.7μm)色谱柱,以0.2%醋酸水溶液(A)-甲醇(B)为流动相进行梯度洗脱,流速1 mL.min-1,紫外检测波长270 nm,柱温30℃。结果:葛根素、大豆苷、甘草苷、野黄芩苷、黄芩苷、汉黄芩苷质量浓度分别在0.1870～93.50μg.mL-1(r=0.9999),0.02730～13.65μg.mL-1(r=0.9999),0.02550～12.75μg.mL-1(r=0.9999),0.05580～27.90μg.mL-1(r=0.9998),0.2124～106.2μg.mL-1(r=0.9999),0.09140～45.70μg.mL-1(r=0.9999)范围内有良好的线性关系;日间、日内精密度变异均小于2%;平均回收率(n=9)分别为101.4%,97.88%,99.15%,99.72%,98.50%,101.4%;稳定性良好。结论:所建立的分析方法操作简便、快速、灵敏,结果准确,重复性好,所需样品少,并已成功应用于葛根芩连汤大鼠肠吸收动力学的研究。     

Absorption and metabolism of hexamethylmelamine and pentamethylmelamine in rat everted perfused gut segments: correlation with in-vivo data

The intestinal oxidative metabolism of hexamethylmelamine (HMM) and pentamethylmelamine (PMM) has been studied in microsomes, isolated mucosal cells and intestinal perfused segments. (sub) Cellular systems revealed an almost equal Km (53-65 microM) and Vmax (5.6-7.0 nmol min-1 g-1 intestine) for both compounds. Detailed studies in everted intestinal perfused segments, showed that HMM is metabolized to a far greater extent than PMM (e.g. 11-times, at 80 microM substrate concentration) while PMM transport was 3 times greater than the transport of unchanged HMM. Only when perfused segments were used as an in-vitro tool was a good correlation observed between the in-vivo and in-vitro rate of intestinal metabolism of HMM and PMM. It is concluded that this is due to preservation of structural integrity of the mucosa for both absorptive and metabolic processes.     

An investigation of the effects of phenobarbitone on the pharmacokinetics of norethindrone in the rat using liver perfusion and everted gut sacs

Previous in vivo studies have suggested that phenobarbitone increases the first pass clearance of norethindrone in the rat by induction of enzymes both in the gut wall and liver. In the present study phenobarbitone caused an increase in both the production of highly polar ether-extractable metabolites and the conjugation of the steroid as it crossed the wall of the everted gut sac preparation. In addition, there was a marked increase in the uptake of norethindrone into the liver followed by increased phase I metabolism in the isolated perfused liver. As expected for a highly cleared drug, enzyme induction had no measurable effect on the terminal half-life of norethindrone in the perfused liver preparation.     

Identifying a selective substrate and inhibitor pair for the evaluation of CYP2J2 activity

CYP2J2, an arachidonic acid epoxygenase, is recognized for its role in the first-pass metabolism of astemizole and ebastine. To fully assess the role of CYP2J2 in drug metabolism, a selective substrate and potent specific chemical inhibitor are essential. In this study, we report amiodarone 4-hydoxylation as a specific CYP2J2-catalyzed reaction with no CYP3A4, or other drug-metabolizing enzyme, involvement. Amiodarone 4-hydroxylation enabled the determination of liver relative activity factor and intersystem extrapolation factor for CYP2J2. Amiodarone 4-hydroxylation correlated with astemizole O-demethylation but not with CYP2J2 protein content in a sample of human liver microsomes. To identify a specific CYP2J2 inhibitor, 138 drugs were screened using terfenadine and astemizole as probe substrates with recombinant CYP2J2. Forty-two drugs inhibited CYP2J2 activity by ≥50% at 30 μM, but inhibition was substrate-dependent. Of these, danazol was a potent inhibitor of both hydroxylation of terfenadine (IC(50) = 77 nM) and O-demethylation of astemizole (K(i) = 20 nM), and inhibition was mostly competitive. Danazol inhibited CYP2C9, CYP2C8, and CYP2D6 with IC(50) values of 1.44, 1.95, and 2.74 μM, respectively. Amiodarone or astemizole were included in a seven-probe cocktail for cytochrome P450 (P450) drug-interaction screening potential, and astemizole demonstrated a better profile because it did not appreciably interact with other P450 probes. Thus, danazol, amiodarone, and astemizole will facilitate the ability to determine the metabolic role of CYP2J2 in hepatic and extrahepatic tissues.     

Development and clinical evaluation of two chromogenic substrate methods for monitoring fondaparinux sodium

This study was designed to develop methods for monitoring of the selective factor Xa inhibitor fondaparinux sodium (ARIXTRA) based on standard laboratory methods for the chromogenic determination of the anti-factor Xa activity of low molecular weight heparin. To examine the biologic activity of fondaparinux in comparison to its plasma concentration, 2 methods were investigated: 1 working with the addition of antithrombin (AT), the other without exogenous AT. Both methods showed a linear relationship of fondaparinux concentration and OD/min on a log-lin scale in the range from 0.1 to 2 microg/mL. Inter- and intra-assay variability was <6% in all cases. The results of spiked samples from patients on vitamin K antagonists (VKA) were in good agreement with both methods, and the determination of the fondaparinux concentration was not influenced by reduced levels of factor X in plasma caused by VKA-intake. Ex vivo samples from orthopedic patients (n=18) on prophylactic treatment with fondaparinux showed concentrations between 0.2 to 0.7 microg/mL 3 hours after s.c. injection. No significant differences were detected between both methods with these samples. The presented methods are suitable tools for monitoring of fondaparinux. The linear calibration curve in the range 0.1 to 2 microg/mL is suitable for determination of prophylactic and therapeutic application of fondaparinux. Both methods, with and without addition of AT, can be performed fully automated in clinical routine on an automated coagulation analyzer (STA coagulation analyzer). No significant differences were detected between both methods with these samples.     

The effect of inhibitors of folic acid absorption on the transfer rate constants in the rat everted proximal jejunum: A method for their evaluation from a three-compartment model

When solute transfer through the intestinal in vitro everted sac preparation is described by a three-compartment system, solute transfer rate constants can be derived for the mucosal and serosal permeability barriers. A catenary variant has been presented as well as a mammillary one where paracellular movement of solute is additionally allowed for. The first order differential rate equations governing the change in solute concentration in all three compartments with respect to time have been solved and the explicit analytical solutions provided. Since these solutions are cumbersome to use in the estimation of the required rate constants, a least squares procedure has been applied directly to the differential form of the rate equations in order to derive the rate constants without recourse to the analytical solutions. Verification of the solutions and of the estimated rate constants was by substitution of the latter into the former to test the goodness of fit for folic acid absorption data. Both variants take into account the simultaneous fluid movement which occurs during absorption experiments and which complicates the interpretation of absorption data. The mammillary model showed that only 10% of folic acid movement could pass directly through the paracellular pathways and that the bulk of folate movement is probably through the epithelial cells. However the catenary model without paracellular movement gave just as good fit to the data and was used subsequently. Experiments investigating the effect of substances implicated in folate malabsorption were analyzed in terms of the catenary model for folic acid absorption, in order to investigate their effects on the transfer rate constants free from the complicating effects on fluid movement. When pronounced inhibition took place, as with methotrexate, the mucosal rate constants were reduced, whereas the serosal rate constants were elevated. Also, the forward (k₁₂) mucosal rate constant correlated significantly with the overall folate transfer in contrast to the other rate constants. These observations are consonant with the concept of a mucosally sited entry step exerting a controlling influence over the transfer rate of folic acid rather than a serosally sited exit process and with the conclusion that this may be the site of action of substances causing folate malabsorption.     

Transport characteristics of 9-nitrocamptothecin in the human intestinal cell line Caco-2 and everted gut sacs

The intestinal absorptive characteristics and the efflux mechanisms of 9-nitrocamptothecin (9-NC), a novel water-insoluble camptothecin (CPT) derivative, were investigated. The Caco-2 cells and the everted gut sacs were used as models of the intestinal mucosa to assess transepithelial transport of 9-NC. The determination of 9-NC was performed by HPLC. In the Caco-2 cells, the absorptive transport of 9-NC was pH dependent and the transport was enhanced at weakly acidic pH on the apical side. No concentration dependence and saturation were observed for the absorptive transport of 9-NC at concentrations up to 250 microM, while secretory transport were concentration dependent and saturable process (K(m) was 49.8 +/- 1.2 microM, V(max) was 38.28 +/- 0.8 ng/cm(2)/min). In the presence of verapamil (100 microM) and CsA (10 microM), potent inhibitors of P-glyprotein (P-gp)/MRP2 (cMOAT), the P(appBL-AP)/P(appAP-BL) ratio was decreased from 3.4 to 1.4 and 1.3, respectively, and permeation of apical to basolateral was enhanced approximately two-fold. In the everted gut sacs, the absorption of 9-NC was passive diffusion and had no significant difference in different gut regions. Adding verapamil in the everted gut sacs over a concentration ranging from 10 to 100 microM, the absorption of 9-NC was significantly enhanced, especially more markedly in lower small intestine (P < 0.05). Overall, the current study suggests that pH and efflux transporters are capable of mediating the absorption and efflux of 9-NC, and they may play significant roles in limiting the oral absorption of 9-NC.     

Effect of calcineurin inhibitor therapy on P-gp expression and function in lymphocytes of renal transplant patients: a preliminary evaluation

Cyclosporine and tacrolimus are substrates and potent inhibitors of the multidrug transporter, P-glycoprotein, in vitro. The authors have investigated the effect of chronic therapy with these and other immunosuppressive drugs on the expression and function of P-glycoprotein in T lymphocytes. Using a P-gp antibody, the authors studied the level of expression of P-gp in CD4 and CD8 T cells over a period of time in renal transplant patients. For comparison, a group of healthy volunteers and patients who did not receive any calcineurin inhibitors but were maintained on mycophenolate mofetil was included. The P-gp expression on lymphocytes from these two groups remained constant (over several months' time). However, patients who were started on tacrolimus or cyclosporine had an initial decline in expression of P-gp on CD4 T cells. Patients who were initiated on calcineurin therapy on day 1 posttransplant also had a decrease in expression of P-gp on CD4 T lymphocytes. This preliminary analysis suggests that the calcineurin inhibitors might be modulating the expression and function of transporters in lymphocytes, thus changing not only the drug concentration but also the apparent efficacy of these drugs. Further understanding and elucidation of such effects would be important in understanding the relationship between pharmacokinetics and pharmacodynamics of these and other drugs, especially for immunosuppressive and anti-AIDS therapy.     

The role of high density lipoproteins in the biodistribution of two radioiodinated probes in the rat

Two radioiodinated probes, 125I-cholesteryl oleate (125I-CO), a derivative of a natural constituent of lipoproteins, and 1-(2-chlorophenyl)-1-(4[125I]iodophenyl)-2,2-dichlorethane (125I-DDD), an analog of the adrenolytic drug o,p'-DDD (mitotane), were selected to study the role of lipoproteins in drug disposition and to examine the ability of these vehicles to direct foreign molecules to specific tissues. In vivo and in vitro techniques were utilized to associate these probes with rat high density lipoproteins (HDL). Tissue distribution studies indicated that prior incorporation of 125I-CO into rat HDL increased the uptake of 125I-CO by rat adrenal, which was dramatically enhanced when this preparation was administered to animals made hypolipidemic with 4-aminopyrazolo(3,4-d)-pyrimidine (4-APP). Acetylation of HDL labeled with 125I-CO provided evidence that the observed uptake into the adrenal was via a receptor-mediated process. In contrast with these results, prior association of 125I-DDD with rat HDL failed to alter the ability of this compound to accumulate in adrenal tissue of normal or hypolipidemic animals. Polyacrylamide gel electrophoresis (PAGE) was utilized to examine the stability of the association of 125I-CO and 125I-DDD with rat HDL. These results suggested that 125I-CO was associated with the lipophilic core of HDL, whereas 125I-DDD appeared to be partially associated with the surface components of HDL. Saturation of surface components with stable o,p'-DDD offered data to suggest that this binding to apoproteins may disrupt the normal receptor-mediated uptake process. These studies indicate that lipoproteins may effect the distribution and tissue uptake of lipophilic compounds and, conversely, lipophilic molecules can effect the metabolic fate of lipoproteins. The overall result is dependent upon the nature of the association of these lipophilic compounds with lipoproteins which is difficult to predict on the basis of molecular structure alone.     

Estimation of absorption parameters from the non-steady-state phase in the rat gut perfusion model

The aim of the study was to calculate absorption parameters, including permeability coefficients (P(app)), from the non-steady-state portion of the outflow to inflow concentration ratio vs time profiles and compare them with those obtained via the more traditionally used steady-state phase. The rat in-situ intestinal perfusion method was used. The compounds studied, diclofenac and macrogol 4000 (polyethylene glycol (PEG) 4000), were perfused at four different flow rates (0.1-2.0 mL min(-1)). The estimates of P(app) from the non-steady-state data were systematically lower for both compounds. The non-steady-state analysis gave estimates of the intestinal radius, r. The internal diameter of the intestine segment increased as the flow rate increased. When this effect was taken into account similar P(app) estimates were obtained by the two approaches. Thus the convention of using a constant value of intestinal radius in the steady-state equation leads to an over estimate of the P(app) when high flow rates are employed. The different trends observed, between P(app) and perfusate flow rate, for the two compounds, macrogol 4000 and diclofenac, may be linked to increased surface area and exposure to membrane pores of larger size. The longitudinal spreading coefficient, De, increased with flow rate and was approximately 1000 times greater than that estimated for molecular diffusion. The high values obtained were consistent with the non-smooth biological surface and peristaltic movement present in-vivo.     

Kinetic characterization of carrier-mediated transport systems for D-glucose and taurocholate in the everted sacs of the rat colon

The present study was aimed at kinetically characterizing the carrier-mediated transport systems for D-glucose and taurocholate in the rat colon, compared with their respective counterparts in the small intestine. The transport of these compounds was evaluated by measuring the initial uptake into everted intestinal tissue sacs. The uptake of both D-glucose and taurocholate was highly saturable, conforming to Michaelis-Menten kinetics without an appreciable nonsaturable transport component. The Michaelis constant (K(m)) was 0.43 and 0.021 mM, respectively, for D-glucose and taurocholate and the maximum transport rate (J(max)) was 0.82 and 0.056 nmol/min/100 mg wet tissue weight (wtw), respectively. For both compounds, these values of K(m) and J(max) in the colon were one to three orders of magnitude smaller than those in the small intestine, suggesting that the transport systems in the colon have by far a higher affinity and a lower transport capacity than their counterparts in the small intestine. However, it is now evident from kinetic studies that carrier-mediated transport systems for D-glucose and taurocholate are also present in the colon. It will be interesting to explore the possibility that they could be used for oral drug delivery via the colon. Their physiological roles would also be of interest.