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Saturable rate of cefatrizine absorption after oral administration to humans.

This study examined the absorption kinetics of cefatrizine, an amino-beta-lactam antibiotic, after oral administration of a single 500-mg dose to 12 healthy volunteers. Plasma concentrations were determined by high performance liquid chromatography. The plots of the percentage of drug unabsorbed and the apparent rate of cefatrizine absorption as a function of time showed, first, a delay and, then, an almost constant rate of absorption with a tendency to move toward first-order kinetics at the end of the process. Three compartmental models incorporating a lag time and first-order elimination kinetics, but differing in their input rate, were used for analysis of the time course of cefatrizine plasma concentrations. The model with first-order absorption kinetics was clearly inadequate. The results were improved with the model for which the rate of absorption is constant, but a model incorporating saturable absorption kinetics of the Michaelis-Menten type improved the fit further. This last model was statistically superior to the constant-rate input model in 6 out of 12 subjects, according to the likelihood-ratio method. Because of the innovative feature of the model incorporating the Michaelis-Menten equation, simulations of the effect of altering the model parameters and the dose administered on the concentration-time profile, were performed. Different hypotheses which might explain why cefatrizine absorption kinetics fits the Michaelis-Menten equation were examined. The observation of saturable absorption kinetics is consistent with a carrier-mediated transport previously reported to occur in the gastrointestinal tract of rats.

Absorption↗

Characterization and effect of phospholipid on bile acid absorption by villi isolated from hamster small intestine.

The effects of phospholipid on absorption of bile acids by hamster small intestine were studied to determine if this compound inhibits absorption of bile acids. Absorption of taurocholic and cholic acids was studied using a new in vitro technique that relates uptake rates to the weight of the villi present on the intestinal sample rather than to the weight of the entire segment of intestine used for the study. This procedure removes from consideration various components of the intestinal wall that are not directly involved with the absorptive process. Using radioactive techniques absorption of each type of bile acid was determined over a broad range of concentrations both in the presence and absence of phospholipid in the incubation medium. Absorption of taurocholic acid by villi from jejunum was determined to be a passive process, as previously reported by others. Villi from ileum absorbed both bile acids by an apparent active process when initial concentrations of bile acids were below 2.0 mM. Above this concentration bile acid absorption by the ileum appeared to be mainly passive. Phospholipid was found to inhibit bile acid absorption by ileum when initial bile acid concentrations were moderately high. However, at low substrate concentration, phospholipid has no appreciable effect on bile acid transport.

Animals↗

Effect of short-chaim fatty acid on sodium absorption in isolated human colon perfused through the vascular bed.

A method of perfusing the isolated human colon in vitro was developed to study the effect of the short-chain fatty acid n-butyrate on sodium absorption under controlled conditions. The isolated colon was viable in vitro provided that ischemia to the colon prior to perfusion was less than 40 min. Viability was judged on glucose utilization, mucosal potential difference, an sodium absorption. Sodium absorption from the lumen was observed either with or without 20 mM n-butyrate. In a control group sodium absorption (nmol/min/cm2 /+- SEM) was 320 /+- 10 (four perfusions, nine observation intervals) and potassium secretion 26 /+- 3 (four perfusions, nine observation intervals). With 20 mM n-butyrate sodium absorption was 1960 /+- 480 (four perfusions, ten observation intervals) (P less than 0.0025). Potassium secretion was 72 /+- 2 (four perfusions, ten observation intervals) and (P less than 0.025). Butyrate absorption was 254 /+- 60 (four perfusions, ten observation intervals) and correlated linearly with the unidirectional flux (Jm leads to S) of sodium (linear coefficient of 0.714, P = less than 0.001). These results suggest that the presence of bacterial short-chain fatty acids may determine the efficiency of sodium absorption in the colon and also indicate that an absence of short-chain fatty acids in the colon could be one factor leading to diminished sodium absorption in the colon of man.

Absorption↗

Intestinal absorption of bile acid glucuronides in rats.

While the intestinal absorption of taurine, glycine, and sulfate conjugates of bile acids has been studied extensively, nothing is known about the absorption of bile acid glucuronides. In the present study, the intestinal phase of the enterohepatic circulation of two bile acid glucuronides was examined. [3 beta-3H]cholic acid 3-O-beta-D-glucuronide or [3 beta-3H]lithocholic acid 3-O-beta-D-glucuronide was perfused through isolated segments of ileum or jejunum with intact blood supply in rats prepared with a biliary fistula. [14C]Taurocholic acid was perfused simultaneously with each glucuronide to compare glucuronide absorption with that of an actively transported bile acid. Intestinal absorption was determined by measuring the rate of secretion of labeled bile acid in bile. The absorption of [3H]cholic acid glucuronide by the ileum and jejunum was one fortieth and one eighth, respectively, that of [14C]taurocholic acid. Comparison of the two glucuronides show that [3H]lithocholic acid glucuronide absorption was 18 and 10 times greater than [3H]cholic acid glucuronide absorption from the jejunum and ileum, respectively. Collectively, the above observations suggest that glucuronidation of bile acids markedly reduces absorption from the small intestine.

Animals↗

Regulation of rat ileal water absorption by central alpha 2 adrenergic receptors.

This study examined the role of central adrenergic receptors in the regulation of water absorption by the rat ileum. Clonidine, an alpha 2-adrenergic receptor agonist, increased water absorption in vivo following intracerebroventricular but not intravenous injection. Intracerebroventricular injection of prazosin, an alpha 1-adrenergic receptor antagonist, did not alter basal water absorption. Prazosin did not prevent the clonidine effect. In contrast, the alpha 2-adrenergic receptor antagonist, yohimbine, reduced basal absorption and prevented the intracerebroventricular clonidine effect. Treatment with reserpine reduced ileal norepinephrine content by 98%, reduced basal water absorption consistent with a loss of sympathetic outflow to the mucosa, but did not prevent the increase in water absorption due to intracerebroventricular clonidine. These results suggest that central alpha 2 receptors regulate water absorption by the rat ileum. The clonidine-induced increase in water absorption is not mediated by the sympathetic nerves innervating the intestine.

Absorption↗

Intestinal adaptation in patients with short bowel syndrome. Measurement by calcium absorption.

Functional adaptation of remaining intestine was evaluated in 30 patients with extensive small bowel resection. Calcium and xylose absorption tests were compared. Calcium absorption was measured by a double-radiotracer technique. Serum xylosemia was measured 2 hr after D-xylose ingestion. Patients were divided into two groups according to the time interval between surgery and evaluation: less (group I) or more (group II) than two years. A statistically significant correlation was found between xylosemia and remaining small bowel length (r = 0.71; P less than 0.001) and between calcium absorption and remaining small bowel length (r = 0.75; P less than 0.001) in group I. A significant correlation was also observed between calcium absorption and time after surgery (r = 0.65; P = 0.001) but not for xylose absorption. Calcium absorption value was significantly increased in group II patients compared with group I patients matched for remaining small bowel length (36.2 +/- 12.5% vs 14.5 +/- 9.1%; P less than 0.001) while no difference was observed between the two groups concerning xylose absorption. These data indicate that intestinal calcium absorption continues to increase for more than two years after a major bowel resection in man. The intestine does not seem to recover all its functions at the same time.

Adaptation, Physiological↗

The effect of systox on rubidium absorption by excised barley leaf tissue.

The influence of various concentrations of the thiol isomer of Systox on Rb absorption by excised barley leaf tissue was compared with the effect of DNP and DCMU. Rb absorption, regardless of the external salt concentration, was progressively reduced as the Systox concentration in the external solution was increased from 0.25 to 1.0 mM. Under anaerobic conditions, light-enhanced Rb absorption by leaf tissue was not influenced by Systox treatments. DNP treatment reduced ion absorption by leaf tissue. In the dark, the relative inhibitory effect of DNP and Systox treatment on Rb absorption was greater than in the light. The combination of Systox plus DNP inhibited Rb absorption more than did separate treatment with either compound. DCMU treatments in the light resulted in a reduction of light-enhanced Rb uptake. Also in the light, the combination of DCMU with Sytox, DNP, or both, inhibited Rb uptake more than did separate treatments of Systox, DNP, or Systox plus DNP. It is suggested that the inhibitory effect of Systox on Rb absorption by leaf tissue is due to partial inhibition of oxidative phosphorylation. Moreover, since light-enhanced Rb absorption is not affected by Systox, it is concluded that Systox has no effect either on the photophosphorylation reactions or on the utilization of high-energy phosphorylated compounds.

Absorption↗

Absorption of isomeric, palmitic acid-containing triacylglycerols resembling human milk fat in the adult rat.

The effect of the positional distribution of palmitic acid (16:0) in triacylglycerols (TAG) on 16:0 apparent absorption in adult rats was investigated. The rats were fed two diets which contained 30 energy % as fat with identical total fatty acid compositions, both containing 30% 16:0. The Betapol diet contained TAG with 73% of total 16:0 in the sn-2 position, the control diet contained TAG with 6% of total 16:0 in the sn-2 position. After six weeks on these diets, the rats were killed two or six hours after the last meal, and the small intestine was removed, cut into 10-cm segments, and the fatty acid composition of the segment's contents was determined. At both time points the amount of 16:0 in the intestinal segments starting at 40 cm from the stomach was much lower in the animals fed Betapol than in the animals fed the control diet. Overall absorption of 16:0 and stearic acid was significantly greater in the Betapol group. Absorption of oleic and linoleic acid from the small intestine was similar in both groups, although the overall absorption was significantly greater in the animals fed Betapol. Total fat absorption was significantly higher in the Betapol-fed rats than in the control-fed rats. No effect on calcium and nitrogen absorption, on plasma total cholesterol and TAG levels, and on bodyweights (growth) was seen. The data demonstrate that the positional distribution of the fatty acids in the TAG molecule affects the site of absorption in the small intestine and particularly the net absorption of saturated fatty acids.

Animal Feed↗

Tissues and organs as indicators of intestinal absorption of minerals and trace elements, evaluated in rats.

Tissue and organ deposition and blood parameters were evaluated as indices of mineral and trace element absorption in rats. The absorption of elements was quantified in relation to nitrogen retention, i.e., considering the weight gain and new tissue synthesis. A rapeseed meal diet was supplied with three levels of calcium, two levels of zinc, and two levels of copper in a factorial design. In general, an increase in dietary mineral content increased the relative absorption, which in turn, increased the tissue deposition progressively. Striated muscle, however, did not respond to either an increased calcium or zinc supply. Furthermore, an increased calcium absorption caused a depression of the fractional phosphorus and magnesium content of femur bones. The copper content of the kidneys and the heart muscle was directly proportional to the amount of absorbed zinc and iron, respectively. The iron content of tissue was, in general, inversely proportional to zinc absorption and showed a tendency to be directly proportional to copper absorption. The zinc level in tissues was, in a similar way, inversely correlated to measured calcium absorption. In conclusion, interactions between elements do not only affect the intestinal element absorption, but also the distribution of already absorbed elements in tissues and organs.

Animals↗

Bioavailability, absorption mechanism, and toxicity of microencapsulated iron (I) sulfate: studies in mice.

The iron compounds used for food fortification have to meet certain requisites related to their bioavailability, absorption mechanism, and toxicity, since they will be consumed by a massive population group. With these purposes, we evaluated a new product used for the iron fortification of milk and lacteous derivatives, called SFE-171, which is a ferrous sulfate, microencapsulated with phospholipids. The bioavailability studies were carried out using four groups of 30 female mice each. In two groups, we studied the absorption of ferrous ascorbate and ferrous sulfate, both in water as reference standards, which show absorptions of 13.1+/-4.9% and 13.2+/-4.3%, respectively. With the third group, we studied the absorption of ferrous sulfate in milk; its value, 7.9+/-3.2%, is significantly lower than that of the remaining groups, with a p < 0.01. The studies with SFE-171 in milk, were performed on the fourth group, with a result of 11.6+/-4.5%, demonstrating that its absorption does not differ significantly from that of the reference standards. The absorption mechanism was determined by means of in vivo self-displacement studies of the ferrous ion and the SFE-171, taking ferrous sulfate as the reference compound. For this study, 210 female mice were used, and no significant difference between the absorption mechanism of both products could be observed. Toxicity studies of the new product with regard to ferrous sulfate were carried out with two groups of 70 female mice each and two groups of 70 male mice each. The lethal dose 50% LD50 for SFE-171 and for ferrous sulfate was 1200 and 680 mg/kg for female mice and 1230 and 670 mg/kg for male mice, respectively, demonstrating that the toxicity of the first product is substantially lower than that of the reference standard. We conclude that the iron product under study has a high bioavailability, an absorption mechanism equal to that of nonhemic iron, and lower toxicity than ferrous sulfate.

Analysis of Variance↗

Absorption profiles of sanchinoside R1 and ginsenoside Rg1 in the rat intestine.

Panax notoginseng is used as a therapeutic agent in Chinese medicine for stopping hemorrhage and also as a general health remedy. Although Panax notoginseng saponins (PNS) are currently attracting attention due to their hemorheological properties, the absorption profiles of PNS have still not been fully investigated. In the present study, an in situ intestinal perfusion rat model was used to investigate the absorption mechanism of sanchinoside R1 (R1) and ginsenoside Rg1 (Rg1), two main components of PNS. Quantitative analysis methods for R1 and Rg1 were first established, then concentrations of R1 and Rg1 in the perfusate were measured in real time through assessment of circulating perfusate in the rat small intestine. The absorption rate constant (k(a)) values for R1 were 0.1223, 0.0946 and 0.0904 h(-1) at a dose of 1, 10 and 100 mg respectively, while those of Rg1 were 0.1169, 0.1134 and 0.1089 h(-1) at a dose of 1, 10 and 100 mg respectively. The optimal absorption site for both of these compounds was found to be the duodenum, which indicated that the bioavailability of the orally administered PNS preparation was relatively low. Finally, the effect of certain absorption promoters on the absorption rates of R1 and Rg1 was investigated. It was found that carbomer and borneol could enhance the permeability of R1 and Rg1 on the intestinal wall (P < 0.05), which indicated that a suitable absorption promoter could improve the absorption of PNS and increase its bioavailability.

Animals↗

Inhibitory effect of wheat fibre extract on calcium absorption in Caco-2 cells: evidence for a role of associated phytate rather than fibre per se.

BACKGROUND: In spite of the strong evidence for the beneficial health effects of dietary fibres, one of the potential nutritional disadvantages of high fibre diets is the adverse effect on the bioavailability of micronutrients, especially minerals and trace elements. With regard to Ca, there is considerable evidence that phytate, which is associated with fibre in many foods, such as cereals and soya products, inhibits Ca absorption. However, there is some doubt as to whether fibres per se have an influence on Ca absorption. AIM OF THE STUDY: Therefore, the purpose of this study was to investigate the effect on Ca absorption of two cereal-based fibre extracts (wheat bran and barley hull). In addition, in order to distinguish between the effect of the fibre components per se and the associated phytate content in these fibre extracts, we investigated the effect of dephytinised wheat and barley fibre extracts and the effect of phytate, as sodium phytate at levels present in the fibre extracts, on Ca absorption. Ca absorption was assessed in Caco-2 cells, as a model for studying Ca absorption in humans. METHODS: The effect of wheat and barley fibre extracts, dephytinised wheat and barley fibre extracts, cellulose, and of sodium phytate on transepithelial 45Ca transport and 45Ca uptake was studied in differentiated Caco-2 cells grown on permeable filter supports. Wheat and barley fibre extracts were dephytinised with wheat phytase. RESULTS: Wheat fibre extract had a 3.2-fold higher phytate content (48.0 mmol/kg) than barley fibre extract (15.1 mmol/kg). Enzymatic dephytinisation of both fibre extracts reduced the phytate content to undetectable levels. The rate of transepithelial 45Ca transport across Caco-2 cell monolayers and the uptake of 45Ca into Caco-2 cells were unaffected by cellulose or barley fibre extract. On the other hand, inclusion of wheat fibre extract in the Ca transport buffer (50 g fibre/l) significantly reduced the rate of 45Ca transport (by 17 and 19% respectively) and the uptake of 45Ca (by 24 and 25% respectively) relative to a fibre-free buffer and a control fibre (cellulose) transport buffer. Increasing the phytate concentration of the transport buffer from 0 to 2 mM (a level close to that in the wheat fibre containing buffer) significantly reduced the rate of 45Ca transport (by 16%) and 45Ca uptake (by 26%). Dephytinisation of the wheat fibre extract removed its inhibitory effects on 45Ca transport and e.g. 45Ca uptake. CONCLUSION: The results from the present study in Caco-2 cells suggest that it is the phytate in wheat fibre extract which is the major inhibitory factor of Ca absorption and that wheat fibre per se has little if any inhibitory effect on Ca absorption. In addition, the results of this study support the usefulness of Caco-2 cells for investigating the effects of dietary factors on the cellular uptake and transepithelial intestinal transport of Ca.

Absorption↗

Time-resolved cutaneous absorption and permeation rates of methanol in human volunteers.

This paper reports on an experimental study of dermal exposure to neat methanol in human volunteers for the purposes of estimating percutaneous absorption rates, permeation kinetics, baseline (pre-exposure) levels of methanol in blood, and inter- and intrasubject variability. A total of 12 volunteers (seven men and five women) were exposed to methanol via one hand for durations of 0 to 16 min in a total of 65 sessions, making this the largest controlled study of percutaneous absorption for this common solvent. In each session, 14 blood samples were collected sequentially and analyzed for methanol. These data were used to derive absorption rates and delivery kinetics using a two compartment model that accounts for elimination and pre-exposure levels. The pre-exposure methanol concentration in blood was 1.7 +/- 0.9 mg 1(-1), and subjects had statistically different mean concentrations. The maximum methanol concentration in blood was reached 1.9 +/- 1.0 h after exposure. Delivery rates from skin into blood lagged exposure by 0.5 h, and methanol continued to enter the systemic circulation for 4 h following exposure. While in vitro studies have reported comparable lag times, the prolonged permeation or epidermal reservoir effect for such miscible solvents has not been previously measured. The mean derived absorption rate, 8.1 +/- 3.7 mg cm-2 h-1, is compatible with that found in the other in vivo study of methanol absorption. Both in vivo absorption rate estimates considerably exceed in vitro estimates. The maximum concentration of methanol in blood following an exposure to one hand lasting approximately 20 min is comparable to that reached following inhalational exposures at a methanol concentration of 200 ppm, the threshold limit value-time weighted average (TLV-TWA). While variability in blood concentrations and absorption rates approached a factor of two, differences between individuals were not statistically significant. The derived absorption and permeation rates provide information regarding kinetics and absorbed dose that can help to interpret biological monitoring data and confirm mathematical models of chemical permeation.

Adult↗

Cellular site of active K absorption in the guinea-pig distal colonic epithelium.

The mammalian distal colon, which is composed of different cell types, actively transports Na, K and Cl in absorptive and K and Cl in secretory directions. To further characterize the K absorption process and to identify the cells involved in K absorption, unidirectional Rb fluxes and luminal Rb uptake into different epithelial cell types were determined in isolated guinea-pig distal colon. Net Rb absorption (1.5-2.5 micromol.h-1.cm-2) was not influenced by inhibition of Na transport with amiloride or by incubating both sides of the epithelium with Na-free solutions, but was almost completely abolished by luminal ouabain, ethoxzolamide or by incubating both sides of the epithelium with Cl-free solutions. Luminal Rb uptake, blockable by luminal ouabain, preferentially occurred in columnar surface and neck cells, to a lesser extent in surface goblet cells and to an insignificant degree in lower crypt cells. Employing a luminal Rb-Ringer (5.4 mM Rb) the Rb concentration increased within 10 min in columnar surface and neck, surface goblet and lower crypt cells to 70, 32 and about 10 mmol. kg-1 wet weight, respectively. The presence of 5.4 mM K in the luminal incubation solution reduced Rb uptake almost completely indicating a much higher acceptance of the luminal H-K-ATPase for K than for Rb. The increase in Na and decrease in K concentrations in surface and neck cells induced by luminal ouabain might indicate inhibition of the basolateral Na-K-ATPase or drastic enhancement of cellular Na uptake by the Na-H exchanger. Bilateral Na-free incubation did not alter Rb uptake, but bilateral Cl-free incubation drastically reduced it. Inhibition of net Rb absorption by ethoxzolamide and inhibition of both Rb absorption and Rb uptake by bilateral Cl-free incubation support the notion that cellular CO2 hydration is a necessary prerequisite for K absorption and that HCO3 leaves the cell via a Cl-HCO3 exchanger. Since ouabain-inhibitable transepithelial Rb flux and luminal Rb uptake rate by surface and neck cells were about the same, Rb(K) absorption seems to be accomplished mainly by columnar surface cells.

Amiloride↗

Why is it challenging to predict intestinal drug absorption and oral bioavailability in human using rat model.

PURPOSE: To study the correlation of intestinal absorption for drugs with various absorption routes between human and rat, and to explore the underlying molecular mechanisms for the similarity in drug intestinal absorption and the differences in oral bioavailability between human and rat. MATERIALS AND METHODS: The intestinal permeabilities of 14 drugs and three drug-like compounds with different absorption mechanisms in rat and human jejunum were determined by in situ intestinal perfusion. A total of 48 drugs were selected for oral bioavailability comparison. Expression profiles of transporters and metabolizing enzymes in both rat and human intestines (duodenum and colon) were measured using GeneChip analysis. RESULTS: No correlation (r(2) = 0.29) was found in oral drug bioavailability between rat and human, while a correlation (r(2) = 0.8) was observed for drug intestinal permeability with both carrier-mediated absorption and passive diffusion mechanisms between human and rat small intestine. Moderate correlation (with r(2) > 0.56) was also found for the expression levels of transporters in the duodenum of human and rat, which provides the molecular mechanisms for the similarity and correlation of drug absorption between two species. In contrast, no correlation was found for the expressions of metabolizing enzymes between rat and human intestine, which indicates the difference in drug metabolism and oral bioavailability in two species. Detailed analysis indicates that many transporters (such as PepT1, SGLT-1, GLUT5, MRP2, NT2, and high affinity glutamate transporter) share similar expression levels in both human and rat with regional dependent expression patterns, which have high expression in the small intestine and low expression in the colon. However, discrepancy was also observed for several other transporters (such as MDR1, MRP3, GLUT1, and GLUT3) in both the duodenum and colon of human and rat. In addition, the expressions of metabolizing enzymes (CYP3A4/CYP3A9 and UDPG) showed 12 to 193-fold difference between human and rat intestine with distinct regional dependent expression patterns. CONCLUSIONS: The data indicate that rat and human show similar drug intestinal absorption profiles and similar transporter expression patterns in the small intestine, while the two species exhibit distinct expression levels and patterns for metabolizing enzymes in the intestine. Therefore, a rat model can be used to predict oral drug absorption in the small intestine of human, but not to predict drug metabolism or oral bioavailability in human.

Animals↗

Selective jejunal hyperabsorption of calcium in absorptive hypercalciuria.

Calcium absorption in the jejunum and ileum of patients with absorptive hypercalciuria was studied by in vivo intestinal perfusion. Net calcium absorption in the jejunum was markedly increased at four luminal calcium concentrations (1 to 20 mM) in the patients with absorptive hypercalciuria when compared to that in normal subjects. In the ileum, net calcium absorption was only slightly increased in the patients with absorptive hypercalciuria. Experiments with radioactive calcium (47Ca) revealed increased unidirectional flux out of the jejunal lumen in the patients but no difference in the unidirectional flux into the lumen, when compared to that in normal control subjects. Net magnesium absorption was normal in the patients. These results suggest that hyperabsorption of calcium in patients with absorptive hypercalciuria is mainly due to enhanced calcium transport in the jejunum and that the defect is specific for calcium since magnesium is absorbed normally.

Adult↗

Intrauterine transfusion: kinetics of absorption of donor cells in fetal lambs.

The absorption of red cells from the peritoneal cavity of fetal lambs was studied in 29 pregnant ewes at approximately 120 days' gestation. Onset of absorption was early, absorption was rapid, and virtually complete absorption was shown in 96% of the fetuses by 92 hours after intrauterine transfusion. The mean time to complete 99% absorption was 75.8 hours, about half the time supposed for human fetuses. The rate of absorption and the maximum level of donor cells in the fetal circulation are both directly related to the transfusion volume. The time required to complete absorption does not vary with the volume transfused: The more blood given at intrauterine transfusion, the faster the fetus absorbs it. This study suggests that absorption in the fetus following intrauterine transfusion is very efficient, and may be faster than previously thought.

Absorption↗

Intestinal active absorption of sugar-conjugated compounds by glucose transport system: implication of improvement of poorly absorbable drugs.

The intestinal absorption of glucose- and galactose-conjugated compounds was studied in the everted sac of the rat small intestine. The absorption clearance of p-nitrophenyl beta-D-glucopyranoside (p-NPglc) at 250 microM in the mucosal side (4.45 +/- 0.34 microL/min/cm, mean +/- SE, N = 4), calculated by dividing the absorption rate by the drug concentration, was significantly decreased (0.476 +/- 0.036 microL/min/cm) in the presence of 1 mM phloridzin, an inhibitor of glucose transport, and in the absence of Na+, a cosubstrate of the glucose transport carrier (0.424 +/- 0.018 microL/min/cm). The absorption clearance of p-NPglc was decreased as its concentration increased. In the same experiment, the absorption clearance of p-nitrophenyl beta-D-galactopyranoside (1.99 +/- 0.23 microL/min/cm) was also significantly decreased in the presence of phloridzin and in the absence of Na+. However, the absorption clearance of p-nitrophenyl beta-D-mannopyranoside (0.811 +/- 0.013 microL/min/cm) was low and not significantly decreased in the presence of phloridzin (P greater than 0.1). Furthermore, the absorption clearance of beta-naphthyl beta-D-glucopyranoside and beta-naphthyl beta-D-galactopyranoside was also significantly decreased in the presence of phloridzin (P less than 0.001). These results indicated that the glucose and galactose moieties provided these compounds with a new route by way of the glucose transport carrier for intestinal absorption.

Animals↗