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PubMed1981

Increase of the intestinal absorption of gentamicin and amikacin by a nonionic surfactant.

This study was concerned with the effect of Cetomacrogol (polyethylene glycol 1000 monocetyl ether), a nonionic surfactant, on the absorption of gentamicin and amikacin from the gastrointestinal tract of rats. A 200-mg dose of Cetomacrogol coadministered orally with 10 mg of gentamicin resulted in a mean peak gentamicin blood concentration of 14.1 microgram/ml, compared with 67.8 microgram/mg when the same gentamicin dose was administered intramuscularly. The area under the curve after administration of the oral mixture was 23% of that after the intramuscular dose. The rectal administration of the mixture resulted in a mean peak gentamicin blood level of 8.2 micrograms/ml, compares to 16.5 microgram/ml when the mixture was administered orally. A 50-mg dose of amikacin coadministered orally with 200 mg of Cetomacrogol resulted in a mean peak amikacin blood level of 13.3 microgram/ml, compared to 310 microgram/ml when this amikacin dose was administered intramuscularly. Cetomacrogol augments the intestinal absorption of gentamicin and amikacin in rats. If the toxicity of the combination in humans is limited, the combination may be potentially clinically useful.

Amikacin↗
PubMed1986

Effect of non-steroidal anti-inflammatory drugs and prostaglandins on the permeability of the human small intestine.

Intestinal permeability was estimated in healthy subjects after ingestion of aspirin (1.2+1.2 g), ibuprofen (400+400 mg) and indomethacin (75+50 mg) at midnight and an hour before starting a 51chromium labelled ethylenediaminetetraacetate absorption test. Intestinal permeability increased significantly from control levels following each drug and the effect was related to drug potency to inhibit cyclooxygenase. Intestinal permeability increased to a similar extent after oral and rectal administration of indomethacin showing that the effect is systemically mediated. Prostaglandin E2 decreased intestinal permeability significantly but failed to prevent the indomethacin induced increased intestinal permeability. These studies show that non-steroidal anti-inflammatory drugs disrupt the intestinal barrier function in man and suggest that the morphological correlates of the damage may reside at the level of the intercellular junctions.

Adult↗
PubMed1981

Gastrointestinal structure and function in Fabry's disease.

We evaluated gastrointestinal structure and function in 13 hemizygous males and 17 heterozygous females, five to 67 years old, from four kindreds with Fabry's disease. Gastrointestinal symptoms, noted in 62% (8/13) of the males and 29% (5/17) of the females, were present prior to the diagnosis of Fabry's disease in five patients; were discovered at the time of study in six patients and were associated with multiple other symptoms in two patients. Serum protein, albumin, folate, Vitamin B12, calcium, phosphorous, cholesterol and iron were normal in all 30 patients. Xylose absorption was normal in 2/2 males and 13/13 females studied. HLA B8 antigen was present in none of the males and 2/17 females. Peroral duodenal (one male), jejunal (six males, two females) and rectal (one male) biopsies on light microscopy demonstrated a normal villous pattern and luxol-fast blue positive "foamy" cell deposits in all males, while no deposits were visualized in the females. In all males and females studied, electron microscopic examination showed electron dense, intralysosomal "zebra-like" (0.5-0.75 micrometer.) bodies in the vascular endothelial and perithelial cells and in the cytoplasm of the small unmyelinated neurons, and perineurial cells. Despite the frequency of gastrointestinal symptoms, both malabsorption and celiac disease were absent.

Adolescent↗
PubMed1983

[Studies on total colectomy, mucosal proctectomy and ileoanal anastomosis (ileoanostomy)].

Studies have been made in order to establish a practical operative procedure of the ileoanostomy as well as to understand its postoperative pathophysiology using 45 patients including 34 with familial polyposis and 11 with ulcerative colitis those which have been followed up for 1 to 4 years. Three major technical problems here with challenged are how to minimize the complications, how to improve the bowel function and how to simplify the procedure. Our J-pouch method was found to have better bowel function compared with those without a pouch and those with H-pouch and also considered to be superior to S-pouch, with its consistent spontaneous evacuation and with a simpler construction. The length of rectal cuff was found to be able to be minimized down to just above the levator muscle without disturbing the bowel function, based on our experiences on two polyposis cases with rectal cancers. The short rectal cuff of about 7-6 cm was considered to be the method of choice for eliminating the cuff abscess in addition to routine use of a diverting ileostomy, and for technical simplification. Ano-abdominal rectal mucosectomy at prone-jack-knife position is recommended to achieve further technical feasibility. The pathophysiological studies including anorectal manometry, intestinal transit time, physical, chemical and bacteriological analysis of the stool, water absorption of the ileal neorectum as well as the systemic metabolic studies supported favorable clinical result of our method. Ileoanostomy by our principle consisting of J-pouch, short cuff and loop-ileostomy, was concluded to be a break through to avoid an abdominal ileostomy after total proctocolectomy.

Colectomy↗
PubMed1991

[Rectal, oral and nasal premedication using midazolam in children aged 1-6 years. A comparative clinical study].

Midazolam is often used for the premedication of children in the pre-school age group. Different noninvasive routes of administration have been described. In a prospective study we compared the effects of oral, rectal, and nasal midazolam in commonly used dosages. PATIENTS AND METHODS. Ninety children undergoing surgery under general anesthesia were assigned to oral (0.4 mg/kg) (MO), rectal (0.5 mg/kg) (MR), or nasal (0.2 mg/kg) midazolam (MN), according to the child's and/or parent's preferred route of administration, after having obtained the parent's informed consent. It was applied on the ward before transport to the operating room. The following parameters were assessed by the observer and the anesthesiologist at different times: sedation, acceptance (child, anesthesiologist), mood, emotion, resistance, pain, nausea and vomiting, blood pressure, and heart and respiratory rates. The Wilcoxon test (P less than 0.05) was used for statistical analysis. RESULTS. All groups were comparable with respect to age, weight, and surgery experience. There was no difference in the anesthesiologist's acceptance of the premedication or the cooperation of the children. The children accepted MO significantly better compared to MN and MR. The fastest onset of sedation was found after MR. Immediately after MN many children became euphoric, and it turned out that the effect of MN was rather euphoric than sedative. The effect of MO was good in many children, but less predictable. This led to a significant delay in transport to the operating room. MO children experienced more nausea and vomiting (P less than 0.05) in the postoperative period. There were no differences in physiological parameters. DISCUSSION AND CONCLUSIONS. The results can be explained by the different characteristics of absorption and patient acceptance. The route of administration according to the child's or parent's choice can be recommended but does not guarantee success. MR had the fastest onset of sedative action due to faster absorption of the drug. MN had a euphoric effect that resulted almost immediately. Oral premedication was best accepted, nasal administration worst. MO produced more side effects than MR and MN in the postoperative period. If the child accepts the rectal route of administration, this should be preferred because of the high success rate and few side effects.

Administration, Intranasal↗
PubMed1980

Studies on microwave and blood-brain barrier interaction.

This investigation was aimed at correlating changes of blood-brain-barrier permeability with the quantity and distribution of absorbed microwave energy inside the brain of adult Wistar rats anesthetized by sodium pentobarbital. Through use of thermographic methods and a direct-contact applicator at the animal's head, the pattern of absorbed microwave energy was determined. Indwelling catheters were placed in the femoral vein and in the left external carotid artery. Evans blue and sodium fluorescein in isotonic saline were used as visual indicators of barrier permeation. Exposure to pulsed 2,450-MHz radiation for 20 min at average power densities of 0.5, 1, 5, 20, 145 or 1,000 mW/cm2, which resulted in average specific absorption rates (SARs) of 0.04, 0.08, 0.4, 1.6, 11.5 or 80.0 mW/g in the brain, did not produce staining, except in the pineal body, the pituitary gland, and the choroid plexus - regions that normally are highly permeable. Except for these regions, staining was also absent in the brains of sham-exposed animals. The rectal temperature, as monitored by a copper-constantan thermocouple, showed a maximum increase of less than 0.75 degrees C from a mean pre-exposure temperature of 36.6 degrees C. The highest brain temperature recorded in a similar group of animals using a thickfilm carbon thermistor was less than 41.0 degrees C.

Absorption↗
PubMed1991

Preparation and evaluation of Eudragit gels. I: Eudragit organogels containing drugs as rectal sustained-release preparations.

New organogels containing salicylic acid, sodium salicylate, procaine, and ketoprofen were prepared by using Eudragit L and S, and propylene glycol. The physical properties (e.g., penetration and extensibility) of the organogels were affected considerably by the incorporation of a basic drug, such as procaine, rather than an acidic drug, such as salicylic acid. In in vivo evaluation using rabbits, it was found that 30% Eudragit L organogels containing 1.25% (w/w) salicylic acid or 2.5% (w/w) ketoprofen showed sustained plasma salicylic acid or ketoprofen levels and almost the same AUC as compared with Witepsol H-15 suppositories containing these drugs. Furthermore, the relative bioavailability for salicylic acid and ketoprofen released from 30% Eudragit L organogels, with 10% (w/w) linolic acid or oleic acid as absorption enhancer, increased to 1.55-1.75- and 1.46-1.85-fold, respectively, compared with 30% Eudragit L organogels without these unsaturated fatty acids.

Acrylic Resins↗
PubMed1988

Pharmacokinetics of two rectal dosage forms of ketoprofen in patients after anal surgery.

Two kinds of dosage forms of commercially available suppositories containing ketoprofen (KP), fatty suppositories (FS) and gelatin capsulated suppositories (GCS), were administered to patients immediately after anal surgery, and results obtained were compared. No difference was found in each corresponding pharmacokinetic parameter of the two dosage forms. However, when these parameters were compared with those from healthy subjects, significant differences were found in the values of peak level (Cmax), peak time (Tmax) and terminal phase half-life (t1/2). Cmax decreased by one half, and Tmax and t1/2 increased two and four times longer, respectively, those from healthy subjects. The absorption rate constant (ka) in patients was significantly (p less than 0.01) smaller than that in healthy subjects. However, the distribution volume/bioavailability (Vd/F), elimination rate constant (kel), and area under the curve (AUC) differed only slightly. Consequently, the flip-flop phenomena could be seen in the time profiles of plasma KP concentration of patients. These results suggested that the rectal suppository of KP should be administered with care, especially in the patients operated on under spinal anesthesia.

Adult↗
PubMed1991

Ion transport abnormalities in rectal suction biopsies from children with cystic fibrosis.

Abnormalities in transepithelial electrolyte transport in cystic fibrosis rectum were analyzed by short-circuit current measurements on 11 control subjects and 11 subjects with cystic fibrosis in a modified Ussing chamber. As judged by the amiloride-sensitive component of the short-circuit current, electrogenic sodium absorption appeared unmodified in cystic fibrosis. In contrast, the short-circuit current response to specific stimuli of both cyclic adenosine monophosphate (cAMP)- and calcium-mediated chloride secretion was drastically altered in all of the cystic fibrosis biopsy specimens examined. Stimulation of the cAMP pathway by 8-bromo cAMP or forskolin resulted in a sustained increase in short-circuit current in control tissues (+ 2.51 +/- 0.63 microA/cm2) but in a slight change in the opposite direction in cystic fibrosis (-0.56 +/- 0.49 microA/cm2; P less than 0.05). Carbachol, a calcium-linked secretagogue, provoked a transient increase in short-circuit current in all of the control tissues (peak response, + 26.69 +/- 3.63 microA/cm2) but a transient change in the opposite direction in 6 of 11 cystic fibrosis tissues (-12.46 +/- 4.64 microA/cm2; P less than 0.05). In 2 of 11 patients with cystic fibrosis, however, a significant but subnormal and transient increase in short-circuit current was observed (+ 2.62 +/- 0.04 microA/cm2; P less than 0.05), whereas in 3 of 11 patients with cystic fibrosis a transient change in the opposite direction (-9.83 +/- 2.20 microA/cm2; P less than 0.05) was followed by a small and transient increase (+ 2.89 +/- 0.83 microA/cm2; P less than 0.05). Using the calcium-mediated secretory response therefore, patients with cystic fibrosis could be divided into two categories: a major population showing defective anion secretion but active cation secretion and a subclass (including three siblings) showing residual but subnormal anion secretion. The easy accessibility of rectal samples and the inversed direction of the cAMP- or calcium-provoked short-circuit current is of considerable advantage in the diagnosis of cystic fibrosis.

Adolescent↗
PubMed2004

Enhanced rectal bioavailability of ibuprofen in rats by poloxamer 188 and menthol.

To improve the bioavailability of poorly water-soluble ibuprofen in the rectum with poloxamer and menthol, the effects of menthol and poloxamer 188 on the aqueous solubility of ibuprofen were investigated. The dissolution and pharmacokinetic study of ibuprofen delivered by the poloxamer gels composed of poloxamer 188 and menthol were then performed. In the absence of poloxamer, the solubility of ibuprofen increased until the ratio of menthol to ibuprofen increased from 0:10 to 4:6 followed by an abrupt decrease in solubility above the ratio of 4:6, indicating that four parts menthol formed eutectic mixture with six parts ibuprofen. In the presence of poloxamer, the solutions with the same ratio of menthol to ibuprofen showed abrupt increase in the solubility of ibuprofen. The poloxamer gel with menthol/ibuprofen ratio of 1:9 and higher than 15% poloxamer 188 showed the maximum solubility of ibuprofen, 1.2mg/ml. Menthol improved the dissolution rates of ibuprofen from poloxamer gels. Release mechanism showed that the release rate of ibuprofen from the poloxamer gels without menthol was independent of the time but the drug might be released from the poloxamer gels with menthol by Fickian diffusion. Furthermore, the poloxamer gel with menthol (poloxamer/menthol/ibuprofen (15%/0.25%/2.5%)) gave significantly higher initial plasma concentrations, C(max) and AUC of ibuprofen than did solid suppository, indicating that the drug from poloxamer gel could be more absorbed than that from solid one in rats. Thus, the poloxamer gel with poloxamer 188 and menthol was a more effective rectal dosage form for ibuprofen.

Administration, Rectal↗
PubMed1987

Rectal infusion of semen results in transient elevation of blood prostaglandins.

Repeated semen deposition in the gut may be linked to the development of viral infections in homosexual men. Other investigators have suggested that rectal insemination may diminish immune responsiveness. We approximated conditions of human insemination by infusing 2 ml of pooled human seminal plasma (SP) into the rectum and/or vagina of rhesus monkeys. This resulted in increased blood plasma concentrations of the bicycloderivative of prostaglandin E (PGEM-II) which reached peak concentrations 2 h after rectal SP instillation in seven of eight test monkeys, but not the controls. The rate of PGE2 diffusion appeared to occur more rapidly across vaginal than rectal mucosa. Suppression of peripheral cellular immune functions was not demonstrated after the single exposure of this study, although persistent and repeat exposures could lead to local or generalized suppression of host defense mechanisms. Absorption of PGE's from the gut may be a cofactor in the development of sexually transmitted viral diseases.

Animals↗
PubMed1972

Effect of luminal ions on the transepithelial electrical potential difference of human rectum.

Skin electrodes are the most convenient reference electrodes for clinical measurements of electrical potential differences (pd) across the epithelium of the alimentary tract but the presence of an electrical charge on normal skin introduces an error. In the present study, by comparison with results obtained using subcutaneous and intravenous electrodes, it was shown that an intradermal injection of saline abolished the skin potential differences. This simple method, therefore, allows skin electrodes to be used to measure the true transepithelial potential differences of gut mucosa. The method was applied to investigate the effect on the rectal potential difference of altering the composition of the luminal solutions. Changes in the cations (sodium, potassium, magnesium) showed that sodium was the most important cationic determinant of the potential difference, especially when sodium absorption was stimulated by giving mineralocorticoids. Changes in the anions (chloride, iodide, bromide, nitrate, bicarbonate, sulphate, phosphate, citrate, and acetate) indicated that the molecular size of the anion rather than its chemical nature was the significant factor and suggested that the ions had to cross a barrier relatively impermeable to anions of radius greater than 3.5 to 4 A degrees . Changes in osmolality and glucose concentration were without effect.

Aldosterone↗
PubMedDate not supplied

[Combined liver and small intestine transplantation in an adult. First case in France. Medical aspects: digestive and nutritional].

OBJECTIVE: We report the digestive, hepatic, intestinal and nutritional history of the first combined liver-small bowel transplantation performed in France in an adult recipient. Currently, the clinical course has been favorable at 30 months. METHODS: In May 1997, a 21-year-old man underwent a double liver-small bowel transplantation for irreversible chronic bowel failure with severe chronic liver disease subsequent to post-surgical short-bowel syndrome. After 28 laparotomies, there were 15 cm of small bowel left for the gastric anastomosis. The patient had a terminal jejunostomy and a left colostomy, excluding a short segment of the transverse colon and the rectum. Total parenteral nutrition including lipids and been initiated in December 1992 (3500 kcal/d) and had led to severe complications. Intestinal absorption before and after the graft were studied with the balance method (input-output) and used bomb calorimetry and measurements of the steatorhhea and creatorrhea. Functional enterocyte mass was assessed from serum citrullin. RESULTS: The postoperative period after the liver-bowel graft (220 cm small bowel with terminal ileostomy and jejunostomy) was uneventful. The immunosuppression protocol included tacrolimus, corticosteroids and azathioprin. One mild episode of acute rejection occurred at day 26 and was controlled with a corticosteroid bolus. No episode of liver rejection occurred. Moderate renal failure regressed partially after reestablishing the fluid-electrolyte balance and adapting tacrolimus dosage. Total parenteral nutrition which had sustained the patient for 4 and a half years was definitely discontinued three months after transplantation. Oral nutrition was initially associated with enteral nutrition (from day 20 to day 90) and became exclusive three months after the transplantation. Intestinal absorption coefficients measured before tranplantation, at 3 months (2200 kcal/d, ileostomy flow 1600 g/d), and at 18 months (2400 kcal/d, ileostomy flow 1300 g/d) post transplantation were, respectively, 22%, 90% and 88% for overall calorie absorption, 25%, 65% and 73% for fat absorption, and 47%, 83% and 67% for nitrogen absorption. At 18 months post-graft, there was a spectacular improvement in the patient's neurological status and his liver function was normal. Endoscopy, radiography, histology, and immunohistochemistry explorations were normal. Ileo-rectal anastomosis was re-established at 23 months post-transplantation. At 30 months the patient is living in his home and on 100% oral nutrition. CONCLUSION: Clinical, nutritional and functional outcome at 30 months in this first French case of liver-small bowel transplantation in an adult recipient has been excellent.

Adult↗
PubMed1990

Aldosterone low-dose, short-term action in adrenalectomized glucocorticoid-substituted rats: Na, K, Cl, HCO3, osmolyte, and water transport in proximal and rectal colon.

The short-term action of aldosterone in physiological concentration on net fluxes of Na, K, Cl, HCO3, osmolytes, and water was examined in the proximal colon and rectal colon of adrenalectomized (ADX) rats in vivo. The measuring time was 12 h, divided in eight periods of 90 min. (a) Aldosterone alone (6 nmol h-1 kg-1) did not stimulate transport in ADX rats. In these experiments plasma [K] increased to fatal values. A basal glucocorticoid substitution of 24 nmol h-1 kg-1 corticosterone caused plasma K to stay constant throughout the experiment, so that epithelial transport was not handicapped by non-specific effects of ADX, but this also did not restore the decreased transport of ADX rats to control values. Under these conditions (absence of aldosterone) in the rectal colon Na and H2O transport was zero, whereas in the proximal colon flux rates were depressed by between 30% and 50%. In contrast, basal glucocorticoid substitution of 18 nmol h-1 kg-1 corticosterone plus infusion of 6 nmol h-1 kg-1 aldosterone caused transport stimulation to values not significantly different from those of non-ADX controls. We conclude that after ADX, aldosterone at physiological concentrations increases transport if, as a prerequisite, a basal glucocorticoid substitution is provided. Transport of Na, K, and H2O is under the total control of aldosterone in the rectal colon but is only moderately altered in the proximal colon.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗