Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Absorption”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,135 records · Page 63Linked to original sources
PubMed1990

Pulmonary absorption of instilled and inhaled DTPA in smokers.

Pulmonary absorption of DTPA (diamine-triethylene-penta-acetic acid) has been widely adopted as an index of pulmonary epithelial permeability. The aim of this study was to analyse: (1) if measurements of pulmonary absorption are influenced by the amount of fluid being administered to the lungs together with the DTPA; and (2) if all DTPA administered to the lungs is equally accessible for pulmonary absorption. To this end DTPA was instilled into a lung segment of six smokers in association with a bronchoscopy. In six other subjects (five smokers and one ex-smoker) the DTPA was inhaled as an aerosol. Pulmonary absorption of DTPA was calculated from the plasma DTPA content, as determined for 4-10 h after the administration of the DTPA. We found that the mean transit time for the absorption of instilled DTPA, t(L), across the pulmonary membranes was significantly (P less than 0.05) longer (median 1498 min, range 955-2636 min) than the t(L) of the absorption of the inhaled DTPA (median 131 min, range 44-512 min). Pulmonary clearance of the inhaled aerosolized DTPA tended to be faster when determined by external detection for 4 h, than when estimated from plasma samples, suggesting that not all pulmonary DTPA may be equally accessible for absorption from the pulmonary lining fluids. We conclude that pulmonary absorption of DTPA is influenced by the volume of fluid being administered to the lungs in association with the measurements. Not all pulmonary DTPA, however, is equally accessible for absorption, rendering external detection of pulmonary clearance of DTPA sensitive to a variety of factors other than pulmonary absorption.

Aerosols↗
PubMed1988

The use of a perfluorochemical emulsion as a vascular perfusate in drug absorption.

In-vitro simultaneous luminal and vascular perfusion using the perfluorochemical emulsion, FC-43 emulsion, as a vascular perfusate, was examined for drug absorption in rat jejunum. The intestinal membrane in this system was found to retain its normal barrier functions for drug transport, as evident from the following: (i) stable absorption clearance of tritiated water and salicylic acid at steady-state, (ii) agreement of this clearance with that by in-situ single-pass luminal perfusion, (iii) active transport of D-glucose and its inhibition by phloridzin and (iv) normal glutamate pyruvate transaminase activity in the intestinal mucosa. FC-43 emulsion gave a more normal absorption site blood flow than the usual vascular perfusate containing erythrocytes and albumin in Krebs-Henseleit bicarbonate buffer solution. Consequently, this emulsion was useful for examining the contribution of blood flow resistance toward drug absorption. The rate-limiting steps of absorption of tritiated water, antipyrine and salicylic acid were examined by perfusion using FC-43 emulsion. The absorption of tritiated water was almost completely blood flow-limited and its absorption clearance may possibly be an approximated absorption site blood flow. The contribution of blood flow resistance to total resistance for antipyrine absorption exceeded that for salicylic acid absorption.

Animals↗
PubMed2002

Superoxide stimulates NaCl absorption by the thick ascending limb.

The thick ascending limb of the loop of Henle (THAL) plays an important role in the regulation of NaCl and water reabsorption. In vivo studies have shown that the free radical superoxide (O) stimulates Na and water reabsorption by the kidney. However, it is not known whether O regulates transport along the nephron in general or in the THAL specifically. We hypothesized that O stimulates THAL NaCl reabsorption. Cl absorption was measured in isolated, perfused THALs from Sprague-Dawley rats. First, we tested whether extracellular O stimulates Cl absorption. Addition of the O-generating system xanthine oxidase/hypoxanthine increased Cl absorption from 112.7 +/- 12.0 to 146.2 +/- 13.9 pmol. mm(-1). min(-1), a 33% increase (P < 0.03). When superoxide dismutase (300 U/ml) was present in the bath, addition of xanthine oxidase/hypoxanthine did not significantly increase Cl absorption (116.9 +/- 13.8 vs. 102.5 +/- 8.5 pmol. mm(-1). min(-1)). Furthermore, adding 200 nM H(2)O(2) to the bath did not significantly affect Cl absorption (from 130.3 +/- 13.7 to 125.3 +/- 19.6 pmol. mm(-1). min(-1)). Because extracellular O stimulated Cl absorption, we next tested whether endogenously produced O could stimulate transport. Under basal conditions, THALs produced detectable amounts of O, as measured by lucigenin-enhanced chemiluminescence. Adding the O scavenger tempol to the bath decreased Cl absorption from 198.1 +/- 35.4 to 132.4 +/- 23.5 pmol. mm(-1). min(-1), a 31% decrease (P < 0.02). To make sure tempol was not exerting cytotoxic effects, we tested whether its effect was reversible. With tempol in the bath, Cl absorption was 117.2 +/- 9.3 pmol. mm(-1). min(-1). Sixty minutes after tempol was removed from the bath, Cl absorption had increased to 149.2 +/- 9.1 pmol. mm(-1). min(-1) (P < 0.05). We concluded that both exogenous and endogenous O stimulate THAL NaCl absorption. To our knowledge, these are the first data showing a direct effect of O on nephron transport.

Animals↗
PubMed2005

Catecholamines potentiate the effect of thyroid hormone on intestinal absorption of glucose in the rat.

The study is to investigate the role of catecholamines on the increased absorption of glucose from the gut by thyroxine, the effect of graded doses of adrenaline and noradrenaline on glucose absorption was studied in euthyroid (ET), hyperthyroid (TH-) and hypothyroid rats (Thx). Glucose absorption was deduced in vivo from intestinal segment perfused with Kreb's bicarbonate solution containing 5.6 mM glucose and in vitro using the everted sac technique. In vivo, basal glucose absorption was significantly increased in the hyperthyroid and decreased in the hypothyroid rats (1.97 +/- 0.19 mM/g, P<0.01, and 0.92 +/- 0.10 mM/g, p<0.05 respectively) when compared with the euthyroid group (1.34 +/- 0.15 mM/g). Adrenaline (20 mg/dl - 80 mg/dl) increased glucose absorption in a dose dependent manner in all the groups. However, the responsiveness of the gut glucose absorption to adrenaline (as evidenced by the dose producing half- maximal absorption or ED50) was reduced by thyroidectomy (ED50 = 26.09 mg/100 ml) and increased by chronic thyroxine treatment (ED50 = 11.13 mg/100 ml). The ED50 in the euthyroid animals was 14.6 mg/100 ml. In vitro, glucose absorption from the isolated segments in both Thx and TH- rats were significantly reduced (P<0.05). Incubation of the isolated intestinal segments with graded doses of adrenaline caused a significan and dose related increases in glucose absorption. However thyroidectomy shifted the dose-response curve for glucose uptake from the isolated intestinal sac incubated with adrenaline to the right of the curve for euthyroid rats. It is concluded that catecholamines may play a role in the increase in intestinal absorption by thyroid hormones.

Animals↗
PubMed1983

Absorption of phosphate in the jejunum of patients with chronic renal failure before and after correction of vitamin D deficiency.

To examine the role of vitamin D in human phosphate absorption, we studied patients with chronic renal disease on hemodialysis, before and after correction of vitamin D deficiency. Thirty-centimeter segments of jejunum were perfused with test solutions containing varying concentrations of phosphate; phosphate absorption rate and electrical potential difference were measured. The data reveal that dialysis patients have depressed phosphate absorption, but the degree of this depression is modest, compared to the extent of their depressed calcium absorption. Therapy with 1,25-(OH)2D3 for 1 wk restored phosphate absorption rate to near normal. With or without 1,25-(OH)2D3 therapy, phosphate absorption was not influenced by calcium in the perfused test solutions. Examination of kinetic data suggests that the vitamin D deficiency of chronic renal failure causes a reduction by half in the rate of active phosphate absorption. By contrast, our data suggest that vitamin D deficiency does not alter passive phosphate absorption. By aspirating jejunal contents after ingestion of different foods, with and without aluminum hydroxide, the physiologic luminal phosphate concentration was found to vary between 0.7 and 12.2 mM. At the lower end of this range, phosphate absorption would be mediated entirely by active transport; at the higher phosphate concentrations, phosphate absorption would be mainly mediated by passive transport.

Adult↗
PubMed1979

[In vitro method for estimation of enteral absorption of clanobutin and other drugs].

Two models have been developed for the determination of in vitro absorption of 4-[4-chloro-N-(4-methoxyphenyl)-benzamidol]-butyric acid (clanobutin) and other agents. Permeability coefficients PM are obtained on artificial phospholipid collodion membranes which permit calculation of absorption coefficients k1 for anticipated human enteral absorption with consideration of physiological parameters. At a pH of 7--8 (small intestine) in particular, k1 shows good agreement with in vitro absorption determined in swine intestine and absorption constant ka derived from pharmacological studies in man. The kinetic absorption model simulates gastro-intestinal transport of the substance as well as local changes in pH. It allows calculation of anticipated human gastric (pH 3) and intestinal (pH 7.5) absorption rates with k1 for different gastric filling volumes. The calculated invasion curves are held against invasion curves calculated from pharmacokinetic studies in man. The comparison shows that all invasion curves calculated according to the kinetic absorption model for gastric filling volumes of 125--1000 ml are within the 95% confidence range; very good agreement exists above all with filling volumes of 125--250 ml. The prognostic value of permeation studies on artificial phospholipid collodion membranes and of the use of the kinetic absorption model in drug design is demonstrated by corresponding studies with chenodesoxycholic acid, indometacin, and clofibrinic acid.

Absorption↗
PubMed1998

The effect of HPMC--a cholesterol-lowering agent--on oral drug absorption in dogs.

The objective of this study was to evaluate the effects which hydroxypropylmethylcellulose (HPMC) may exert on oral drug absorption, in cases where this soluble fiber is administered to regulate blood lipid levels. Studies were conducted in vitro and in healthy female mongrel dogs using two different grades of HPMC, i.e. K8515 HPMC and ultra high molecular weight (UHMW) HPMC. The maximum plasma concentration, Cmax, of paracetamol and both the Cmax and the area under the concentration-time curve, AUC, of cimetidine were significantly decreased by the coadministration of 10 g of K8515 HPMC or 7.5 g of UHMW HPMC dissolved in 500 mL normal saline under fasting conditions. No statistically significant effects were observed on hydrochlorothiazide or mefenamic acid absorption. Based on in vitro data and previous studies it appears that reductions in gastric emptying and dissolution rate of paracetamol account for the effect observed in vivo. For cimetidine, a drug which can be absorbed from both the small and the large intestine, the indigestibility of HPMC in the colon in addition to the great reduction of dissolution rate led to reductions of both the Cmax and AUC values. The long Tmax values, even in the absence of HPMCs and the more modest reduction of the dissolution rate of hydrochlorothiazide by the HPMCs are thought to have precluded the observation of any significant alterations in the in vivo absorption profile. Owing to its erratic absorption, no statistically based conclusion could be drawn about the effects of coadministered HPMC on the oral absorption of the poorly soluble mefenamic acid. It is concluded that the effects of HPMCs on drug absorption in dogs are most pronounced for compounds with absorption profiles that are dependent on gastric emptying, i.e. compounds that are highly water soluble and that exhibit short Tmax values. Compounds with long absorption profiles appear to be less susceptible to changes in absorption behavior due to coadministration of HPMCs.

Animals↗
PubMed2000

Reflection and absorption of millimeter waves by thin absorbing films.

Reflection, transmission, and absorption of mm-waves by thin absorbing films were determined at two therapeutic frequencies: 42. 25 and 53.57 GHz. Thin filter strips saturated with distilled water or an alcohol-water solution were used as absorbing samples of different thicknesses. The dependence of the power reflection coefficient R(d) on film thickness (d) was not monotonic. R(d) passed through a pronounced maximum before reaching its steady-state level [R(infinity)]. Similarly, absorption, A(d), passed two maximums with one minimum between them, before reaching its steady-state level [A(infinity)]. At 42.25 GHz, A(d) was compared with absorption in a semi-infinite water medium at a depth d. When d < 0.3 mm, absorption by the film increased: at d = 0.1 mm the absorption ratio for the thin layer sample and the semi-infinite medium was 3.2, while at d = 0.05 mm it increased up to 5.8. Calculations based on Fresnel equations for flat thin layers adequately described the dependence of the reflection, transmission, and absorption on d and allowed the determination of the refractive index (n), dielectric constant (epsilon), and penetration depth (delta) of the absorbing medium for various frequencies. For water samples, epsilon was found to be 12.4-19.3j, delta = 0.49 mm at 42.25 GHz, and epsilon = 9.0-19.5j, delta = 0.36 mm at 53.57 GHz. The calculated power density distribution within the film was strongly dependent on d. The measurements and calculations have shown that the reflection and absorption of mm-waves by thin absorbing layers can significantly differ from the reflection and absorption in similar semi-infinite media. The difference in reflection, absorption, and power density distribution in films, as compared to semi-infinite media, are caused by multiple internal reflections from the film boundaries. That is why, when using thin phantoms and thin biological samples, the specifics of the interaction of mm-waves with thin films should be taken into account.

Absorption↗
PubMed2002

Biochemical evidence for transcytotic absorption of polyaspartamide from the rat lung: effects of temperature and metabolic inhibitors.

Airway-to-perfusate polyhydroxyethylaspartamide (PHEA) absorption was studied in the isolated perfused rat lung at a reduced temperature and by the use of metabolic inhibitors, to kinetically clarify the mechanisms and cellular pathways of its active absorption. Fluorophore-labeled PHEA (F-PHEA; 7.4 kDa) was administered into the airways, and its absorption followed with time at 25 degrees C and in the presence of 2,4-dinitrophenol (DNP), ouabain (OUA), monensin (MON), and nocodazole (NOC). Across-dose absorption profiles were analyzed using a kinetic model incorporating active (V(max,P) and K(m,P)) and passive (k(a,P)) absorption from the pulmonary lung region alongside the competing, pulmonary-to-bronchial mucociliary escalator (k(E)). The model was validated at 25 degrees C and a lack of perturbation on the k(a,P) and k(E) values for passively absorbed solutes confirmed by studying the disposition of sodium fluorescein and 4.4 kDa fluorescein isothiocyanate-labeled dextran. F-PHEA absorption was significantly suppressed at 25 degrees C, compared with 37 degrees C, because of a significant decrease in the value of the maximum rate of active absorption, V(max,P) (4.37 --> 0.67 microg/min; p < 0.05), whereas the carrier-affinity term, K(m,P), was statistically unchanged. F-PHEA's active absorption was also significantly inhibited by DNP (> or =0.5 mM), OUA (> or =50 microM), MON (> or =10 microM), and NOC (> or =1 microM), whereas these inhibitors had no significant effect on the values for k(a,P) and k(E). Thus, F-PHEA's pulmonary active absorption in the rat lung was temperature- and adenosine 5'-triphosphate-derived intracellular energy-dependent (DNP and OUA inhibition) and apparently mediated via transcytosis through cytoplasmic endosomes and microtubules (MON and NOC inhibition).

2,4-Dinitrophenol↗
PubMed1989

A pharmacokinetic model for the percutaneous absorption of indomethacin and the prediction of drug disposition kinetics.

A pharmacokinetic model with two parallel absorption processes from two fractions has been derived for the percutaneous absorption of indomethacin. The simulation includes five first-order rate constants assigned the following significance: (a) rapid absorption (ka1) and slow absorption (ka2) through the skin; and (b) distribution into the tissue and subsequent elimination from the body. The model, applied to data obtained after percutaneous dosing of ointments under occlusion, successfully described the plasma profile observed in the presence and absence of laurocapram (Azone) and sorbitan monooleate. The penetration characteristics through stripped skin were also well described by the model. It was clarified that indomethacin was absorbed via both pathways, with rapid and slow absorption rate constants at the initial time stage, and via the latter pathway at the later period. Also, laurocapram and sorbitan monooleate increased the fraction absorbed via the rapid absorption pathway by about three times, without a significant alteration of either absorption rate constant, while the enhancers gave no significant effect on either absorption pathway in the stripped skin. The results suggest that the model is simple yet adaptable enough to prove of general use for the interpretation of percutaneous absorption data.

Animals↗
PubMed1994

Temperature dependence of the absorption coefficient of water for midinfrared laser radiation.

The dynamics of the water absorption peak around 1.94 microns was examined. This peak is important for the absorption of holmium and thulium laser radiation. To examine the effect of temperature on the absorption coefficient, the transmission of pulsed Ho:YAG, Ho:YAG, Ho:YSGG, and Tm:YAG laser radiation through water of 22 degrees C, 49 degrees C, and 70 degrees C was measured as a function of the thickness of the water layer. From these data the absorption coefficients were determined at the three wavelengths. We found that at all three wavelengths, the absorption coefficients decreased when increasing the temperature. Second, the absorption spectrum of water was measured from 1,850-2,150 nm with a spectrophotometer. It was found that the absorption peak at 1.94 microns (at 22 degrees C) shifts to shorter wavelengths with increasing temperatures, to 1.92 microns at 70 degrees C. A model was developed to predict the temperature distribution incorporating the dynamic change in absorption coefficient. The temperature distributions are compared to the predictions of a model assuming constant optical properties. It is shown in this study that the dynamics of the absorption coefficient has a significant influence on the expected zone of damage and ablation parameters in the 2-microns wavelength range.

Absorption↗
PubMed1997

Absorption of retinol from the retinol:retinol-binding protein complex by small intestinal gut sheets from the rat.

Absorption of retinol by the absorptive cells of the small intestine is a necessary first step in the metabolism of vitamin A. Previous studies had suggested that absorption of retinol from the retinol:retinol-binding protein complex (retinol:RBP) might be receptor mediated. We investigated the specificity of this process by determining the absorption of retinol from retinol:RBP by small intestinal sheets obtained from the suckling rat. We found that the absorption of retinol from retinol:RBP was a saturable process. Unlike the absorption of free retinol, absorption of retinol from retinol:RBP was not inhibited by N-ethylmaleimide. The absorption was specifically competable by unlabeled retinol:RBP and by both apo- and holocellular retinol-binding protein, but not by beta-lactoglobulin. This suggests that a specific mechanism is present for the absorption of retinol bound to RBP.

Animals↗
PubMed1999

Estimation of dermal absorption using the exponential saturation model.

Estimates of dermal absorption are used in exposure assessment to calculate the internal dose of persons contacting pesticides and are a critical part of risk assessments. An exponential saturation model with lag time was validated against a classic dermal absorption study of 12 pesticides administered to human volunteers. The model gave dermal absorption estimates consistent with reported values in the literature. Moreover, this model gave more realistic estimates of the percentage of dermal absorption for some pesticides, which have special properties. In most submitted dermal absorption studies in animals, especially rats, "bound" skin residues (BSR) at treated skin sites were generally high when animals were sacrificed more than 24 h after the dose was administered. The direct addition of the total BSR as an absorbed dose would likely overestimate actual dermal absorption. From a well-conducted dermal absorption study, this model can be utilized to estimate maximum excretion of the administered dermal dose as a result of further absorption of bioavailable BSR. Resulting dermal absorption estimates are appropriate for regulatory purposes in the risk assessment of pesticides because they take into account the bioavailability of BSR while at the same time the estimates are not overly conservative.

Animals↗
PubMed2002

Dermal absorption in rhesus monkeys of polychlorinated biphenyls from soil contaminated with Aroclor 1260.

Human health risk assessments involving contaminated soil include dermal absorption as a potential pathway contributing to the total exposure burden. For PCB-contaminated soil, the U.S. Environmental Protection Agency uses a dermal absorption factor of 14%, based on a 1993 study of dermal absorption in rhesus monkeys. The current study examined several parameters that can influence the dermal absorption of lipophilic hydrocarbons, including soil organic content, particle size, skin residence time, and contaminant "aging" in the soil. Four groups of four female rhesus monkeys each were exposed to radiolabeled Aroclor 1260 either intravenously (100% absorption) or dermally with PCB-spiked soil. Groups exposed for 12 or 24 h to PCBs aged in soil exhibited percutaneous absorption values of 3.43 +/- 0.35 and 4.26 +/- 0.52%, respectively, while a group exposed for 24 h to soil freshly spiked with PCBs exhibited a dermal absorption value of 4.07 +/- 0.46%. Evidence strongly suggests that the factor most responsible for modulating the percutaneous absorption of highly lipophilic compounds from soil is its organic content. The base soil used in the current study with Aroclor 1260 had an organic content of 5-6% (< or =2 mm particle fraction), a value typical for U.S. soil. The organic content of the soil applied to the skin was 8.7% (<150 microm particle fraction), a value that contrasts sharply with the soil containing 0.9% organics used in the 1993 study with Aroclors 1242 and 1254 that produced a dermal absorption value of 14% for PCBs.

Administration, Cutaneous↗
PubMed1987

The effect of dietary amino acids on the gastrointestinal absorption of melphalan and chlorambucil.

Previous studies have demonstrated that the bioavailability of melphalan and chlorambucil may be reduced under non-fasting conditions, and that the gastrointestinal and cellular absorption of melphalan is an active process, while that of chlorambucil is passive. In view of these findings, the effect of dietary amino acids on the gastrointestinal absorption of these two drugs was investigated using the in situ rat intestine model. The segment lengths used in the study were (mean +/- SD) 47.1 +/- 3.8 cm. Experimentation was carried out in a randomised fashion and involved monitoring the absorption of drug from control intestinal segments and from segments perfused with L-glycine (1 and 10 mM) and L-leucine (1 and 10 mM). For chlorambucil, absorption was carried out from segments perfused with the 10 mM concentration of amino acids only. Aliquots of gut-perfusing solution were removed at 5-min intervals over 30 min and assayed for drug content using a high-performance liquid chromatography (HPLC) method which was selective for each agent. Values recorded for the absorption of melphalan were (mean +/- SD percentage absorption per centimetre segment length over a 30-min period) 1.11% +/- 0.07% cm-1 (control); 1.18% +/- 0.20% cm-1 (1 mM L-glycine); 0.99% +/- 0.27% cm-1 (1 mM L-leucine); 0.80% +/- 0.25% cm-1 (10 mM L-glycine); and 0.60% +/- 0.23% cm-1 (10 mM L-leucine). Chlorambucil absorption from control animals was 1.77% +/- 0.11% cm-1 gut length, as against 1.77% +/- 0.08% cm-1 in 10 mM L-glycine and 1.69% +/- 0.16% cm-1 in 10 mM-L-leucine-perfused segments. The only statistically significant observation was a reduction in melphalan absorption from perfusate containing 10 mM leucine (P less than 0.005). The experimental data suggest that competitive inhibition by amino acids may be one of the mechanisms involved in the observed reduction in melphalan bioavailability under non-fasting conditions, but that it has no effect on chlorambucil absorption.

Amino Acids↗
PubMed1995

Gastrointestinal calcium absorption and dietary calcium load: relationships with bone remodelling in vertebral osteoporosis.

Patients with vertebral osteoporosis have a wide range of bone loss rates, bone remodelling rates and capacities for gastrointestinal (GI) calcium absorption. To test the hypothesis that variations in GI absorptive capacity determine rates of bone loss or remodelling, we have sought relationships between calcium absorption or vitamin D metabolite levels on the one hand and rates of cancellous and cortical bone loss (measured by serial quantitative computed tomography in the radius; n = 25) or indices of bone remodelling in tetracycline-prelabelled transiliac biopsies (n = 41) on the other, in a sequential untreated group. Calcium absorption (net and true) was measured in 18-day balances and by a two-isotope deconvolution method (fractional absorption and maximum absorption rate, MAR). There was no significant seasonal effect on any of these four measures of calcium absorption (variance ratio, F = 0.52-1.61, p > 0.1) or on 1,25-dihydroxyvitamin D levels (F = 0.13, p > 0.1; range 11-69 pg/ml), notwithstanding the expected seasonal effect on 25-hydroxyvitamin D levels (mean 18.7 ng/ml, zenith mid July, semi-amplitude 7.5 ng/ml; F = 6.82, p < 0.01). Neither this metabolite nor 1,25-dihydroxyvitamin D correlated with any index of calcium absorption (p > 0.1). No measure of calcium absorption (or intake) had a significant relationship with radial cortical or cancellous bone loss (p all > 0.1) but cancellous bone loss was associated with the rate of endogenous calcium excretion (r = 0.50, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1996

Effects of somatostatin on luminal transit and absorption of nutrients in the proximal gut of minipigs.

A discrepancy exists on the effects of somatostatin on the absorption of nutrients: in humans, absorption was found to be reduced, whereas in rats no effects were observed. However, intestinal absorption might be influenced by the transit rate of contents. This was not considered in previous studies. Therefore, we investigated simultaneously the effects of somatostatin on the absorption of nutrients and on luminal transit. In five minipigs (44-62 kg), a 150-cm segment of the proximal jejunum was temporarily isolated by two cannulas and perfused with an oligomer diet (60% carbohydrate, 18% protein, and 22% fat). The perfusion rate was 2 kcal/min. Flow rate and mean transit time were determined by markers (Cr-EDTA and Cu-EDTA). Somatostatin was infused intravenously at rates of 0.5, 1.25, 2.5, and 5 micrograms/kg/hr. In control experiments saline was administered intravenously. Somatostatin dose-dependently diminished flow rate of luminal contents and increased the transit time. At the largest dose of somatostatin (5 micrograms/kg/hr) flow rate was reduced by 50% compared with control infusion of saline (1.0 +/- 0.4 vs 2.0 +/- 0.05 ml/min, P < 0.05), and transit time was increased 3.6-fold (39.8 +/- 4.7 vs 11.2 +/- 4.9 min; P < 0.05). Somatostatin also dose-dependently enhanced the absorption of nutrients and energy. However, the increase in absorption was small compared with the effects on flow rate and transit time. At the largest dose (5 micrograms/kg/hr) absorption of energy, carbohydrate, protein, and fat was enhanced only by 9.7%, 7.0%, 5.2%, and 15.3%, respectively (49.9 vs 40.2%, 50.9 vs 43.9%, 67.3 vs 62.1%, and 30.1 vs 14.8% during saline infusion; P < 0.05). Results indicate that the major effects of somatostatin consist in a marked reduction of flow rate and a delay of luminal transit. The small increase in absorption was caused by the delay in transit and the prolonged contact of the nutrients with the mucosa. Therefore, in absorption studies, effects on transit need to be considered.

Analysis of Variance↗
PubMed1996

New perspectives on the theory of permeability and resistance in the study of drug transport and absorption.

Permeability coefficient (P) expressed as distance per unit time has been commonly interpreted to represent the velocity of drug movement across a heterogeneous medium such as skin and intestinal epithelium. The basis of such an interpretation is questioned on several grounds. For example, the basic assumption for calculating P (as defined conventionally) according to the Fick's law of diffusion requires the entire medium to be homogeneous and rate-limiting in transport. The theoretical basis of the widely used total resistance or resistance additivity concept is reviewed. Such a concept is shown to be applicable to the study of total transit time across the medium but may not be applicable to the study of steady-state flux or absorption across the medium under normal conditions. Based on the diffusional, compartmental, absorptive clearance or carrier-mediated-transport analysis it is shown that only the first transport resistance from the bulk medium across the surface (such as cellular membranes) of the permeation medium (such as a cell or a tissue) is usually the deciding factor in drug transport or absorption. Resistances on the other side of the surface barrier usually only affect the drug accumulation vs. time profile in the medium, but not the steady-state flux or absorption. The role of unstirred water layer adjacent to the internal capillary wall is postulated to play an important role in causing the blood-flow dependency in absorption, a phenomenon that cannot be rationalized by the conventional effective permeability concept. The conventional concept of sink conditions on the serosal side is questioned. The present analysis further supports the use of the absorptive or transport clearance concept in absorption or transport study. Effective permeability is regarded as a mathematical operator for transport across a barrier or a tissue, and may be unrelated to the Fick's law of diffusion under most conditions. The velocity unit for P is regarded simply as a "collapsed" unit based on the absorptive or transport clearance per unit gross surface area. It is hoped that this commentary will stimulate further research and discussions in this general area of drug transport and absorption. It appears that there is a need to experimentally confirm the total resistance theory in biological systems.

Cell Membrane Permeability↗