Rectal Absorption Research Articles

Transmucosal fluid movement and its effect on rectal sulfanilamide absorption in rat.

Sulfanilamide absorption from the rectum in rats was studied using the recirculating perfusion method with perfusion solutions having different levels in tonicity by changing concentration of sodium chloride and revealed that the absorption was influenced by the apparent transmucosal bidirectional fluid movements.

Studies of absorption of suppositories. VIII. Effect of the amount of base on absorption of sulfonamides from rabbit rectum.

To investigate the effect of the amount of a base on the absorption of drugs from the rectum, amount of rectal fluid and distribution region of a drug in the rectum after administration of a suppository were determined. The distribution region of a drug in the rectum increased in proportion to the volume of suppository, both in PEG and cacao butter base, The rectal fluid increased with increasing volume of the PEG base, but concentration of the base in rectal fluid was always about 30%, independent of the base volume, at 2 hr after administration. On the other hand, there was no detectable amount of the fluid but a little mucus in the rectum after administration of cacao butter suppository. The results of blood concentration studies showed that both the rate and extent of absorption of sparingly soluble sulfonamides were enhanced by the increasing amount of PEG and cacao butter base. The absorbability of water-soluble sulfonamide was reduced by the increased volume of PEG base, and a better absorbability of a soluble sulfonamide was obtained from cacao butter than from PEG base. The results of in vitro membrane permeation experiment with isolated gut segments served sufficiently to explain the influence of the amount of base on in vivo rectal absorption of sulfonamides. From the results of in vivo and in vitro experiments, it was concluded that rectal absorption of sulfonamides from increased base volume of suppository depended mainly on the increment of the distribution area, that is, absorption area in rectum.

Absorption and distribution of radioactivity from suppositories containing 3H-benzocaine in rats

AbstractThe effects of the suppository vehicle, drug concentration, and nonionic surfactants on in vitro benzocaine dialysis through a cellulose membrane and on rectal absorption in rats of total radioactivity following administration of 3H-benzocaine were investigated. In vitro dialysis correlated quite well with in vivo absorption, and drug release was greater from water-soluble vehicles than from oleaginous vehicles. Inclusion of a nonionic hydrophilic or lipophilic surfactant in cocoa butter resulted in a statistically significant increase for in vitro drug release, while a lipophilic surfactant showed little effect in vivo and a hydrophilic surfactant depressed release in vivo. Both types of surfactant had small effects on release from polyethylene glycol. In vitro release of benzocaine from some commercially available suppositories was compared with experimental preparations. Variation in blood radioactivity following administration of the same concentration of 3H-benzocaine in the same dosage form in male and female rats is reported.

Influence of Particle Size on Rectal Absorption of Aspirin

The rectal absorption of aspirin from theobroma oil suppositories was studied in seven human subjects using urinary excretion measurements. The effect of particle size on the excretion rate and cumulative amount of total salicylate excreted was demonstrated by the administration of a 600‐mg dose as powdered aspirin and as aspirin disks having 0.023 as much surface as powdered aspirin. In vitro dissolution profiles of aspirin from the suppositories were studied. By the NF XIII Method II, the time required for 50% of the aspirin to dissolve from the suppository was 50 and 100 min for the powdered aspirin and the aspirin disks, respectively. In the bioavailability study, the diffusion equilibrium was attained at approximately 4–5 and 9–10 hr after the rectal administration of powdered aspirin and aspirin disks, respectively. No correlation was found between bioavailability and the dissolution profiles as determined by the USP XVIII dissolution method.

Rectal Absorption From Aspirin Suppositories in Children and Adults

Absorption of salicylate was determined by means of urinary excretion techniques after rectal administration of a commercial aspirin suppository to eight children and four adults. The absorption of drug from the suppository was exceedingly slow; perhaps an order of magnitude slower than that observed after oral administration of conventional tablets. The amount of drug absorbed was highly dependent on the time between insertion and the first defecation (retention time ). Retention times as long as four to five hours resulted in only about 60% of the dose being absorbed. In our judgment the use of aspirin in the form of rectal suppositories provides the clinician with little control over drug therapy.

Influence of Vehicle Dielectric Properties on Acetaminophen Bioavailability from Polyethylene Glycol Suppositories

The rectal absorption of acetaminophen from an aqueous solution and from several polyethylene glycol base dosage forms was studied in six human subjects using urinary excretion measurements. A relationship was observed between acetaminophen bioavailability and the dielectric properties of the vehicles utilized. The in vitro dissolution rates of acetaminophen in these dosage forms were also studied and were somewhat related to the time of occurrence of the maximum urinary excretion rate.

Correlations between In Vitro Transport in a Three-Phase Model Cell and In Vivo Absorption of a Series of Sulfanilamides

A three-phase model cell, employing a liquid lipid barrier, was used to establish correlations between reported in vivo absorption data and experimentally determined in vitro transport rates for a series of N1-substituted heterocyclic sulfanilamides. These studies, using isopentyl acetate as the lipid phase, involved the effect of pH on the rate constants for three derivatives and the effect of the N1-substituent on the overall transport for unionized species. Correlations were made between the in vitro data and in vivo gastric, intestinal, and rectal absorption data, indicating the utility of this model to simulate passive drug absorption. Transport rates and partition coefficients were also found to be related.

Letter to the Editor

In answer to Dr. Weiss' inquiry, aminophylline was specifically delivered intravenously to maintain control of the rate and dosage administered. Since rectal absorption is irregular, varies from preparation to preparation, and may often be associated with over-dosage, especially in the poorly hydrated child who is vomiting, we neither advocate nor condone rectal aminophylline. The last two fatal cases of aminophylline toxicity in our community occurred in young patients who were given injudicious doses of aminophylline rectally as outpatients.

Salicylate Absorption from Rectal Suppositories

The absorption in humans of aspirin and sodium salicylate incorporated in six suppository bases was studied by means of urinary salicylate elimination. It was found that the rectal dose of aspirin and sodium salicylate was equivalent to the oral dose. Rectal absorption was altered by pharmaceutical factors, which affected the release of the drug from the suppository. Aspirin was rapidly released from suppositories of polyethylene glycol and polyoxyethylene (4) sorbitan monostearate with glyceryl monostearate; aspirin was poorly released from a suppository of sorbitan monopalmitate. Sodium salicylate was rapidly released from a suppository of theobroma oil. Data for the release from theobroma oil suppositories containing cholesterol and glyceryl monostearate were inconclusive.

Effect of Vehicle Dielectric Properties on Rectal Absorption of Acetaminophen

The rectal absorption of acetaminophen from an aqueous suspension, a propylene glycol suspension, and a theobroma oil suppository was measured by urinary excretion. The results are discussed in terms of their relationship to the dielectric constants of the vehicles.

Theoretical Model Studies of Drug Absorption and Transport in the Gastrointestinal Tract II

Multicompartment diffusional models for the absorption of neutral, acidic, basic, and amphoteric drugs were investigated. The general model consisted of a bulk aqueous phase, an aqueous diffusion layer,n-compartments of homogeneous and heterogeneous phases, and a perfect sink. With the mathematical techniques reported previously, equations were derived in general terms for the nonsteady- and steady-state periods. Utilizing the steady-state diffusion efficiency function of the barrier systems, the first-order rate constants for various examples of two- and three-compartment models were obtained from the general model and some computations were given. Various sets of in situ experimental rat data have been analyzed by means of the different models. These include the intestinal, gastric, and rectal absorption of sulfonamides and barbituric acid derivatives. Self-consistent dimensional constants and diffusion coefficients were arrived at and the correlations obtained with the models have been found to be generally satisfactory.

Hormonal control of excretion in the american cockroach, II. preliminary purification of a diuretic and antidiuretic hormone

a 1. 1. An in vitro rectal preparation has been devised which allows the measurement of lumen volume changes by the isotope dilution technique. 2. 2. This sensitive assay provided the necessary accuracy to determine small changes incurred when dilute endocrine samples from column chromatography were usedas the hormone. 3. 3. A diuretic hormone of a molecular weight greater than 30,000 and an antidiuretic hormone of about 8000 have been partially purified by gel filtration on columns of P-30 polyacrylamide. 4. 4. The purification scheme indicates that contaminates of low molecular weight are present in the terminal abdominal ganglion which could be released in the intact animal and also modify rectal water absorption.

Influence of sodium on calcium transport by the rat small intestine.

Influence of sodium on calcium transport by the rat small intestine.

Absorption and excretion of drugs. XL. Enhancement of the rectal absorption of pharmaceutical amines with lauryl sulfate and saccharinate anions.

The absorption of ion pair complexes was studied in rats by means of in situ rectal perfusion technique. Two combinations, sodium lauryl sulfate-basic drugs and saccharin sodium-basic drugs were examined in detail. The disappearance from the perfusate of both components were determined in order to elucidate the mechanism of ion pair absorption. Basic drugs except some quaternaries tested were absorbed much faster in the presence of lauryl sulfate and saccharinate anions but the converse could not be applied for the anionic components. Blood level analyses of basic drugs also demonstrated such absorption enhancement effect. Enhancement of the absorption of cationic drugs could better be related to the binding behavior of those drugs to the rectal mucosal preparations than their apparent chloroform or benzene/water partition coefficients.

Evidence for antidiuretic control of rectal water absorption in the cockroach Periplaneta americana L.

An in vitro method has been devised for the study of water absorption by the cockroach rectum. The method permits measurement of the amount of water absorbed over a period of time. Passive water movement occurs across the rectal wall. Water absorption appears to occur from isosmotic and hyperosmotic trehalose solutions, and is DNP sensitive. Water absorption by recta from dehydrated animals was compared with that of recta from hydrated animals. Recta from dehydrated animals absorbed water at a higher rate than recta from hydrated animals. This is interpreted as an antidiuretic response, and indicates that the cockroach possesses a regulatory system to control rate of rectal water absorption. Dehydration of cockroaches produced by lowering the r.h. of the atmosphere, by supplying with hyperosmotic saline, or by withholding water gave similar results. Extracts of various insect tissues were applied to in vitro recta to determine if factors were present which affect rate of water absorption. Extracts of corpora allata, metathoracic ganglia, and last abdominal ganglia from hydrated animals produced an increase in rate of water absorption. When the same tissues were taken from dehydrated animals, their extracts had less activity. However, brain extracts from dehydrated animals produced an increase in water absorption. These results indicate that rate of rectal water absorption may be regulated by a factor or factors of neuroendocrine origin.

Absorption and Excretion of Drugs. XXIX. Effect of Surface-active Agents on Rectal Absorption of Sulfisoxazole from Oily Base

Effect of various types of surface-active agents on the rectal absorption of sulfisoxazole from cocoa butter was investigated by the blood level determination with rabbits. Blood levels were in general increased with increase of surface-active agent, and decreased by addition of the large amount. Surface-active agent accelerated the release of the drug from the base to dissolution medium. On the other hand, surface-active agent reduced the absorption rate of the drug from aqueous solution. These results suggest that the increase of the drug absorption at the low concentrations of surface-active agents is due to release acceleration, but the reduction effect on drug absorption in their higher concentrations is due to predominance of absorption reduction over release acceleration. Cetyltrimethyl ammonium bromide especially stimulated the drug absorption in the very low concentrations.

Absorption and excretion of drugs. 28. Rectal absorption of sulfonamides from oily solutions

In order to clarify the mechanism of rectal absorption of sulfa drugs from fatty oils, this absorption was examined by perfusion of rat rectum with fatty oils of different nature, using higher fatty acids, their esters, and higher alcohols. Absorption rate of sulfisoxazole becomes greater as the drug in the fatty oil becomes more easily liberated into the excretion fluid. Absorption rate of sulfapyridine is not affected greatly by the nature of fatty oils, while that of sulfathiazole becomes smaller with fatty oils from which the drug is more easily liberated into the excretion fluid. These results seem to indicate that drug absorption from fatty oils takes two different processes ; that of absorption through the rectal membrane after being liberated into the excretion fluid and that absorbed directly from the fatty oil through the rectal membrane.

Absorption and excretion of drugs. XXV. On the mechanism of rectal absorption of sulfonamides.

The rates of absorption of several sulfonamides were measured in the rectum of the anesthetized rat. Their absorption was considerably affected by the pH of solution. The unionized form was in general readily absorbed, while the ionized form was more slowly absorbed. Sulfonamides which are highly lipid-soluble were more readily absorbed than those which are poorly lipid-soluble. And there is a slightly acidic zone at the rectum-blood barrier, like the intestinal-blood barrier. The results suggest that sulfonamides are absorbed from the rectum by a passive transport, and that the patterns of absorption in the rectum are similar as a gastro-intestinal absorption of drugs. When the permeability constants were plotted against the absorption velocity constants, the good agreement was obtained among the spots. The diffusion constant as well as lipid-solubility is an important factor for rectal absorption.

Absorption and excretion of drugs. XXVI. Effect of water-soluble bases on rectal absorption of sulfonamides.

The rates of absorption of sulfonamides were measured in the presence of a number of water-soluble bases. The absorption rates was reduced by these bases. This reduction depends mainly upon their decrease of lipid-vehicle partition. The differences existed in their absorption at incorporating the various water-soluble bases, and these differences are related to the dielectric constants of the bases : the larger their dielectric constant, the smaller the reduction of rectal absorption. The results suggest that the drug abosrption in the presence of water-soluble bases can be interpreted by the depression of the polarity in the vehicle.

Absorption and excretion of drugs. XXVII. Effect of nonionic surface- active agents on rectal absorption of sulfonamides.

The rectal absorption of sulfonamides were reduced by the addition of various nonionic surface-active agents. This reduction depends upon the entrapment of drug in micelles. The drug in micelles was also absorbed a little, and therefore the enhancement of drug absorption were obtained by solubilization of the drug remained as a solid in solution. The mechanism of drug absorption in the presence of nonionic surface-active agent can be explained by the concept that there are two ways of the passage of the free drug and of the drug in micelles.