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PubMedDate not supplied

Pseudoephedrine absorption from controlled release formulations: absorption rate constant estimation methods.

Five methods of absorption rate (Ka) estimation were compared using data from a previously reported bioavailability study: Wagner-Nelson (WN), asymptotic WN (AWN), the Hendeles-Weinberger modification of the WN (HW), nonlinear regression performed on plasma concentration vs time data with fixed elimination rates (NL), and nonlinear regression performed on the cumulative sum of AUCs obtained during WN analysis (AUCNL). The maximum plasma concentration (Cmax) and the time at which Cmax occurred (Tmax) were predicted with each method's respective Ka's, and these were compared to observed values. The WN and HW were consistently biased in their predictions of Cmax and Tmax, providing slower Ka's than any of the other methods. AWN could only be used for the reference treatment. Both NL and AUCNL provided unbiased estimations, but AUCNL had a high level of imprecision. With this set of data, only NL was an acceptable method for accurately estimating Ka.

Adult↗
PubMed1999

A computer-controlled system to simulate conditions of the large intestine with peristaltic mixing, water absorption and absorption of fermentation products.

This paper introduces a new type of system to simulate conditions in the large intestine. This system combines removal of metabolites and water with peristaltic mixing to obtain and handle physiological concentrations of microorganisms, dry matter and microbial metabolites. The system has been designed to be complementary to the dynamic multi-compartmental system that simulates conditions in the stomach and small intestine described by Minekus et al. [Minekus M, Marteau P, Havenaar R, Huis in't Veld JHJ (1995) ATLA 23:197-209]. High densities of microorganisms, comparable to those found in the colon in vivo, were achieved by absorption of water and dialysis of metabolites through hollow-fibre membranes inside the reactor compartments. The dense chyme was mixed and transported by peristaltic movements. The potential of the system as a tool to study fermentation was demonstrated in experiments with pectin, fructo-oligosaccharide, lactulose and lactitol as substrates. Parameters such as total acid production and short-chain fatty acid (SCFA) patterns were determined with time to characterize the fermentation. The stability of the microflora in the system was tested after inoculation with fresh fecal samples and after inoculation with a microflora that was maintained in a fermenter. Both approaches resulted in total anaerobic bacterial counts higher than 10(10) colony-forming units/ml with physiological levels of Bifidobacterium, Lactobacillus, Enterobacteriaceae and Clostridium. The dry matter content was approximately 10%, while the total SCFA concentration was maintained at physiological concentrations with similar molar ratios for acetic acid, propionic acid and butyric acid as measured in vivo.

Absorption↗
PubMed1996

Percutaneous absorption of ketoprofen. I. In vitro release and percutaneous absorption of ketoprofen from different ointment bases.

Ketoprofen (KP) is a potent non-steroidal anti-inflammatory drug which is used for the treatment of rheumatoid arthritis. The oral administration of KP can cause gastric irritation and renal adverse effects. Topical application of the drug can bypass gastrointestinal disturbances and provide relatively consistent drug levels at the site of action. Since the efficacy of an ointment depends on the type of ointment base and the concentration of the drug, four different bases (white petrolatum, cold cream, hydrophilic ointment and Carbopol 940 gel) were used at 1, 3, 5, 7 and 10% concentrations of KP to evaluate the effect of ointment base and concentration. The general rank order of the drug release was found to be: Carbopol gel > hydrophilic ointment > cold cream > white petrolatum. There was a positive correlation between the concentration of KP and release rate for all bases except Carbopol gel. The in vivo percutaneous absorption of KP from different ointment bases at 3% concentration was studied by carrageenan-induced paw edema in mice. The rank order of the percent edema inhibition was as follows: Carbopol gel > or = hydrophilic ointment > cold cream > white petrolatum. There was a good correlation between the in vitro and in vivo results.

Animals↗
PubMed2001

Silicic acid (Si(OH)(4)) is a significant influence upon the atomic absorption signal of aluminium measured by graphite furnace atomic absorption spectrometry (GFAAS).

We have identified silicic acid (Si(OH)(4)) as an important modifier of the absorbance signal of aluminium measured by graphite furnace atomic absorption spectrometry (GFAAS). The presence of Si(OH)(4) enhanced the signal by as much as 50%. The extent of the enhancement was dependent upon both [Al] and [Si(OH)(4)] and was maximal when [Al]< or =4.44 micromol dm(-3) and [Si(OH)(4)]> or =0.50 mmol dm(-3). The enhancement of the Al absorbance signal was not linearly related to [Si(OH)(4)] and the effect was, generally, saturated, for all [Al] tested, at [Si(OH)(4)]> or =0.50 mmol dm(-3). Si(OH)(4) was significantly more effective in enhancing the Al absorbance signal than Mg(NO(3))(2). However, the co-occurrence of 10 mmol dm(-3) Mg(NO(3))(2) and 2 mmol dm(-3) Si(OH)(4) in samples abolished the enhancement due to Si(OH)(4). The presence of Si(OH)(4) in samples could result in an overestimation of the Al content of those samples by as much as 50%. Errors in the measurement of Al in samples containing Si(OH)(4) could be prevented using matrix-matched calibration standards. Our observation could have serious implications for the determination of Al in aqueous samples of both geochemical and biological interest. It may also point towards the application of Si(OH)(4) as a novel and effective matrix modifier in the determination of Al by GFAAS since the inclusion of Si(OH)(4) in standards and samples improved the limit of detection of Al from ca 8 nmol dm(-3) to 3 nmol dm(-3).

Absorption↗
PubMed2005

Innershell absorption spectroscopy of amino acids at all relevant absorption edges.

The C, N, and O K-edge near-edge X-ray absorption fine structure spectra of the 22 most common proteinogenic alpha-amino acids in the zwitterionic form collected from solvent-free polycrystalline powder films in the partial electron yield mode are reported. Spectral features common to all amino acids, as well as distinctive fingerprints of specific subgroups of these compounds, are presented and discussed.

Absorption↗
PubMed1992

Intestinal absorption of peptides and peptide analogues: implications of fasting pancreatic serine protease levels and pH on the extent of oral absorption in dogs and humans.

In order to describe and predict the impact of intestinal metabolism on peptide absorption, intestinal chymotrypsin activity, flow rate, and pH were characterized in fasted, duodenally fistulated dogs as a function of gastrointestinal (GI) motility phase. GI motility was classified as either active or quiescent. Cumulative volume, F(t), and volumetric flow rate, Q(t), curves were constructed and the data were sorted according to motility phase. The mean +/- SE active phase pH was 6.4 +/- 0.3, whereas the quiescent phase pH was 7.3 +/- 0.3. The difference between the mean active and the mean quiescent phase pH values was significant. The active and quiescent phase flow rates (ml/min) were also significantly different, at values of 1.2 +/- 0.2 and 0.28 +/- 0.07, respectively. The active phase flow rates were consistent among the dogs studied; however, the quiescent phase flow rates were highly variable among the dogs. The variability of the quiescent phase flow rates was expected since phase II of the GI motility cycle is characterized by intermediate, irregular spike activity. The mean active and quiescent phase chymotrypsin activities were 1.87 x 10(-5) +/- 0.53 x 10(-5) and 1.56 x 10(-5) +/- 0.65 x 10(-5) M, respectively. The active phase values were not statistically different among dogs, however, the quiescent phase values were found to be highly variable among dogs. The difference between the active and the quiescent phase chymotrypsin mean levels, however, was not statistically significant. The chymotrypsin levels determined in dogs were found to be approximately 10 times greater than those reported in humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed2001

Dietary lactulose decreases apparent nitrogen absorption and increases apparent calcium and magnesium absorption in healthy dogs.

To study the effect of lactulose on the route of nitrogen excretion, we fed six healthy, adult dogs on diets containing either 0, 1 or 3 g lactulose/MJ metabolizable energy according to a 3 x 3 Latin square design. The results were analysed to identify statistically significant linear trend effects of lactulose. Faecal pH was significantly lowered by lactulose. Faecal ammonium and nitrogen excretion tended to be raised by lactulose feeding whereas urinary urea excretion was significantly reduced. Lactulose feeding significantly lowered apparent nitrogen digestibility. It is concluded that lactulose feeding shifts nitrogen excretion from urine to faeces in dogs which may be beneficial for liver patients. The data are in line with the concept that lactulose stimulates bacterial growth in the colon which in turn enhances faecal nitrogen excretion and lowers the entry of colonic ammonia into the bloodstream, leading to a lesser workload for the liver and less urinary nitrogen excretion. Lactulose consumption was also found to produce a dose-dependent increase in the apparent absorption of calcium and magnesium, but not phosphorus.

Animals↗
PubMed1982

Decreased intestinal calcium absorption in vivo and normal brush border membrane vesicle calcium uptake in cortisol-treated chickens: evidence for dissociation of calcium absorption from brush border vesicle uptake.

The influence of cortisol on intestinal calcium transport was studied in isolated duodenal loops and brush border membrane (BBM) vesicles of vitamin D-deficient or replete chickens. Four- to five-week-old vitamin D-deficient cockerels were dosed intraperitoneally with 1 microgram of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] alone 15 hr before sacrifice or in combination with 1, 3, or 5 mg of cortisol 24 and 48 hr before sacrifice. After a 1-microgram dose of 1,25-)OH)2D3 the in situ intestinal ligated loop technique revealed a 60% increase in calcium absorption compared to control birds (P less than or equal to 0.001). However, the administration of cortisol in various doses (3 and 5 mg) to chickens given 1,25-(OH)2D3 resulted in significant decreases in intestinal calcium transport in vivo (P less than or equal to 0.05; P less than or equal to 0.05). When intestinal BBM vesicles were prepared from birds treated in a manner identical with that described above, there was no observable difference between calcium uptake in BBM vesicles of the 1,25-(OH)2D3-treated birds and that of the cortisol plus 1,25-(OH)2D3-treated birds. 1,25-(OH)2D3-treated and 1,25-(OH)2D3 plus cortisol-treated chicks had intestinal BBM vesicle uptakes that were significantly greater than those of vitamin D-deficient controls (P less than or equal to 0.02; P less than or equal to 0.025). These data show that in vivo intestinal calcium transport may be markedly reduced in the presence of normal intestinal BBM vesicle calcium uptake. This suggest that factors other than BBM calcium uptake (e.g., protein synthesis or contraluminal membrane events) play an important role in the movement of calcium from the intestinal lumen into the bloodstream and extracellular fluid of the organism.

Animals↗
PubMed1989

Measurement of non-haem iron absorption in non-anaemic rats using 59Fe: can the Fe content of duodenal mucosal cells cause lumen or mucosal radioisotope dilution, or both, thus resulting in the underestimation of Fe absorption?

Male Wistar rats (188 g) were fed on a semi-synthetic (SS) diet (38 mg iron/kg) ad lib. for 7 d and then meal-fed for 1 d. After a 21 h fast each rat was given one meal (10 g) of high-Fe SS (500 mg Fe/kg; high-Fe group) or control (38 mg Fe/kg; control group) diet. After 16 h 2 ml of an 59Fe-labelled ferrous sulphate solution (18 kBq 59Fe; 120 micrograms Fe) was administrated by gavage and equal numbers of rats from each group were killed 6 or 24 h after dosing. Mucosal uptake of 59Fe from the gut lumen and transfer of 59Fe from mucosa into the carcass were measured. Total Fe content of the duodenum was also determined. Mucosal 59Fe uptake and transfer were markedly lower in the high-Fe group compared with the control group. The Fe content of the duodenum, the major region of Fe absorption, was significantly greater in the high-Fe group than in the controls. A larger amount of Fe may thus have been released into the lumen of the high-Fe rats, via mucosal cell turnover, resulting in a greater lumen dilution of the 59Fe dose in this group compared with the controls. Calculations are presented which demonstrate that such an effect could not possibly account for the observed difference in mucosal 59Fe uptake between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1978

[Nitrogen and amino acid absorption in swine. 3. Endogenous secretion and absorption of nitrogen].

The endogenous nitrogen in the duodenum and the distal segment of the small intestine of 3 fistulated pigs fed a 15-N-labelled feed protein was determined using the isotope dilution technique. Over 24 hours, the endogenous N secretion was found at least 12.5 g at the end of the duodenum. For the upper segment of the small intestine, a statistically secured correlation between endogenous nitrogen and chyme amount was found to exist. It was possible to determine the true and apparent absorption of the nitrogen for both individual segments of and the whole digestive tract.

Amino Acids↗
PubMed2001

Drug absorption may be delayed after stroke: results of the paracetamol absorption test.

BACKGROUND: Autonomic changes are frequent after stroke but it is not known whether gastric emptying is altered. We have investigated this using the paracetamol absorption test. METHODS: 12 acute stroke patients and 13 healthy controls of similar age received 1 g oral paracetamol tablets. We studied all patients within 24 h of the stroke and 5 days later. Standard pharmacokinetic measurements were derived from the plasma paracetamol-time curve. RESULTS: In acute stroke patients, mean plasma T(max) was delayed compared with that in controls (96.3 vs 46.2 min, P=0.015). The C(max) of paracetamol was also lower (16.1 vs 23.9 mg l(-1), P=0.028). The area under the curve of paracetamol did not differ significantly in acute stroke patients and controls. CONCLUSIONS: Gastric emptying appears to be delayed in acute stroke patients, and this may result in delayed pharmacological action of orally administered drugs.

Acetaminophen↗
PubMed2001

Hydroxypropyl-distarch phosphate from Tapioca starch reduces zinc and iron absorption, but not calcium and magnesium absorption, in rats.

Male rats were fed a fiber-free, purified diet containing either gelatinized tapioca starch that was not modified chemically (TS, 50 g/kg diet) or gelatinized chemically modified tapioca starch (CMS, 50 g/kg) for 21 d. TS was used as the control. The six kinds of gelatinized hydroxypropyl distarch phosphate (HDP) from tapioca with two different degrees of substitution (DS) and three different degrees of cross-linking (DC) were used as CMS sources. The wet weight and moisture of fecal output of the rats fed HDP with higher DS were 100 and 20% greater than that in the control rats, respectively. The weights of cecal wall and cecal contents were also 30 and 50% higher in the rats fed HDP with higher DS than those in the control rats. The pH of the cecal contents was more acidic in the rats fed HDP with higher DS than that in the control rats. Fecal excretion of bile acids was 40% higher in the rats fed HDP with higher DS than in the control rats. These effects of HDP were only slightly affected by the DC. The plasma cholesterol concentration was 16% lower in the rats fed HDP with higher DS and highest DC than in the control rats. The concentrations of liver lipids and plasma triglycerides and the cecal pool of organic acids were not affected by diet. The apparent absorptions of Ca and Mg were not affected by diet, but those of Zn and Fe were 75 and 70% lower in the rats fed HDP with higher DS than in the control rats. These results suggest that the physiological effects of HDP depend on the DS but not on the DC.

Animals↗
PubMed1989

Folic acid absorption determined by a single stool sample test--a double-isotope technique. The folic acid absorption capacity in children.

The fractional folic acid absorption (FAFol) was determined in 66 patients with various gastrointestinal diseases by a double-isotope technique, employing a single stool sample test (SSST) as well as a complete stool collection. The age of the patients ranged from 2.5 months to 16.8 years (mean 6.3 years). The test dose was administered orally and consisted of 50 micrograms of [3H]folic acid (monoglutamate) (approximately 20 muCi), carmine powder, and 2 mg 51CrCl3 (approximately 1.25 muCi) as the unabsorbable tracer. The whole-body radiation given to a 1-year-old child averaged 4.8 mrad only. The stool and napkin contents were collected and homogenized by the addition of 300 ml chromium sulfuric acid. A 300-ml sample of the homogenized stool and napkin contents, as well as 300 ml chromium sulfuric acid (75% vol/vol) containing the standards, were counted for the content of 51Cr in a broad-based well counter. The quantity of [3H]folic acid was determined by liquid scintillation, after duplicate distillation. Estimated by SSST, the FAFol, which employs the stool with the highest content of 51Cr corresponding to the most carmine-colored stool, correlated closely with the FAFol based on complete stool collection (r = 0.96, n = 39, p less than 0.0001). The reproducibility of FAFol determined by SSST was assessed from repeated tests in 18 patients. For a mean of 81%, the SD was 4.6%, which corresponded to a coefficient of variation of 5.7%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1979

The absorption of cimetidine before and during maintenance treatment with cimetidine and the influence of a meal on the absorption of cimetidine--studies in patients with peptic ulcer disease.

1 The absorption of a single oral dose of cimetidine taken on a fasting stomach or together with a meal was studied in 28 patients before and during 12 weeks treatment with cimetidine. 2 No significant changes in bioavailability were seen during treatment measured as the area under the blood concentration curve (AUC). 3 AUC after a single dose of 400 mg cimetidine was 2.05 times the area after a 200 mg dose. 4 There was a good correlation between AUC and the dose of cimetidine given corrected for body weight (r=0.89). 5 There was no difference in bioavailability if 200 mg cimetidine was taken on a fasting stomach or together with a beef steak meal. 6. During fasting conditions there was a peak in blood concentration at about one hour followed by a second unexplained peak during the third to fifth hour after dose administration. 7 With food the initial rise in blood concentrations was slower and there was only one peak occurring about 2 h after dose administration.

Adult↗
PubMed1976

Inhibitory effect of eggs on vitamin B12 absorption: description of a simple ovalbumin 57Co-vitamin B12 absorption test.

Ovalbumin and egg yolks, mixed separately in vitro with radiocyanocobalamin (57 Co-vitamin B12), were served to normal volunteers in a cooked form. Ovalbumin, and to a lesser degree, egg yolks were observed to inhibit vitamin B12 absorption. This observation explains the rather poor assimilation of vitamin B12 from eggs labelled in vivo with 57 Co-vitamin B12.

Absorption↗
PubMed1993

Enteral absorption of octreotide: absorption enhancement by polyoxyethylene-24-cholesterol ether.

1. The somatostatin octapeptide-analogue octreotide was absorbed as an intact peptide from the gastro-intestinal tract with an absolute bioavailability of about 0.3% in rats. Administration of octreotide in the presence of polyoxyethylene (24)-cholesterol-ether (POECE) resulted in an about 23 fold increase of bioavailability. 2. In vitro studies with Caco-2 cells showed a dose-dependent increase in octreotide permeation with increasing doses of coadministered POECE. The use of [3H]-polyethyleneglycol (PEG) 4000 as an extracellular marker also indicated that higher doses of POECE may partly enhance paracellular transport of macromolecules. 3. By means of fluorescence microscopy it was shown that transepithelial transport of the fluorescent octreotide analogue (4-nitrobenzo-2-oxa-1,3-diazol [NBD] labelled octreotide) was enhanced by the addition of POECE. Besides an increased enterocyte uptake, there was evidence of enhanced partition of NBD-octreotide into the intercellular space between enterocytes after co-administration of POECE. In addition, there appeared to be changes in the hepatic topographic disposition of NBD-octreotide when it was given together with POECE compared with its administration alone. 4. In a study in healthy volunteers, 16 mg POECE significantly enhanced by 8 fold the absorption of octreotide after oral administration.

4-Chloro-7-nitrobenzofurazan↗
PubMed1978

Absorption of sodium benzylpenicillin from the equine uterus after local Lugol's lodine treatment, compared with absorption after intramuscular injection.

Plasma concentrations of sodium benzylpenicillin following intrauterine infusion were increased by reducing the volume of solution and expelling air from the vagina after infusion. Instillation of 10 per cent Lugol's iodine solution into the uterus before penicillin infusion further increased the absorption rate, although peak plasma levels of penicillin were less than half those which resulted from intramuscular injection of the same dose.

Absorption↗
PubMed1995

Small intestinal absorption of bropirimine in rats and effect of bile salt on the absorption.

The intestinal absorption characteristics of a poorly water-soluble drug, bropirimine, were investigated by the in-situ small intestinal loop method using male Sprague-Dawley rats. Bropirimine in solution was well absorbed in the overall small intestine, following first-order kinetics. The rate determining step for the disappearance of bropirimine from the small intestinal loop after dosing in the suspension was the dissolution process from suspension. Bropirimine was solubilized by sodium glycocholate. The disappearance of bropirimine from the small intestinal loop was suppressed by sodium glycocholate contained in the solution, because of the loss of thermodynamic activity of bropirimine after its involvement in the micellar complex, not by the direct effect of bile salt on the permeability of intestinal mucosa. The disappearance of bropirimine was also suppressed by sodium glycocholate contained in the suspension. The suppression by sodium glycocholate seemed to be caused by the greater influence of sodium glycocholate on the thermodynamic activity of bropirimine than on the dissolution from suspension.

Adjuvants, Immunologic↗