Rectal Absorption Research Articles

The Effects of Salicylate on the Rectal Absorption of Phenylalanine and Some Peptides, and the Effects of These Peptides on the Rectal Absorption of Cefoxitin and Cefmetazole

The disappearance of phenylalanine and phenylalanylglycine from a perfusate circulated across rat rectal tissue was enhanced significantly in the presence of salicylate or 5-methoxysalicylate at pH 4.5, 7.4, and 8.5. The disappearance of di-, tri-, and tetraphenylalanine from a perfusate at pH 7.4, although facilitated by the presence of salicylate and 5-methoxysalicylate, was also fairly substantial when no adjuvant was present. These peptide analogues of phenylalanine also enhanced the rectal absorption of cefoxitin and cefmetazole, two highly water soluble antibiotics. Phenylalanine and phenylalanylglycine, both poorly absorbed across the rectal membrane when administered alone, did not enhance the rectal absorption of either antibiotic.

The Effect of PH on Rectal Absorption in Ulcerative Proctocolitis

The Effect of PH on Rectal Absorption in Ulcerative Proctocolitis

Rectal versus oral absorption of diflunisal in man

Rectal absorption of diflunisal from various dosage forms was studied in man. The rectal dosage forms included fatty and macrogol suppositories, an aqueous suspension and solutions with various solvents in order to achieve complete dissolution of diflunisal. A comparison was made with an orally administered suspension. The plasma concentrations of diflunisal were measured by means of HPLC analysis after a single dose of 250 mg diflunisal in a cross-over study in 7 volunteers.Compared with oral administration, rectal absorption conditions are limited as a consequence of the poor solubility characteristics of diflunisal. Therefore attempts were made to improve absorption conditions by varying the nature of the rectal dosage form. The addition of alkali and solvents such as polyethylene glycol and glycofurol, did result in an increase of the rate of absorption, whereas the bioavailability 8 h after administration did rise up to 80% as compared with oral dosing. In the case where suppositories are employed, a fatty vehicle rather than a water-soluble base should be chosen in order to stimulate the driving force for absorption. It is concluded that 500 mg diflunisal suspended in a 4 ml fatty mass results in peak plasma concentrations comparable with an oral dose of 250 mg diflunisal.

The Effect of Ph on Rectal Absorption in Ulcerative Proctocolitis

The Effect of Ph on Rectal Absorption in Ulcerative Proctocolitis

Rectal absorption of metronidazole from polyethylene glycol suppositories.

The rectal absorption of metronidazole from an aqueous suspension, a fatty suppository and three different polyethylene glycol suppositories was studied in healthy volunteers and compared with absorption from an oral solution. Rectal absorption was found to be rather slow for all suppositories. Of all rectal dosage forms, the polyethylene glycol suppositories gave the highest peak plasma levels and the highest relative bioavailability. Compared with oral administration, a relative bioavailability of 80% could be obtained.

Effect of adjuvants on the rectal absorption and lymphatic uptake of pepleomycin in rats.

The rectal absorption of pepleomycin sulfate (PEPS) in rats was increased significantly by the coadministration with each of diclofenac (DC), sodium 5-methoxysalicylate (5-MSA) and phenylalanine enamine of ethylacetoacetate (Enamine). 5-MSA increased the lymphatic uptake of PEPS after rectal administration while DC and Enamine did not. The mechanism behind the enhancing action of 5-MSA on the lymphatic uptake of PEPS may be due to the suppressing action of 5-MSA on the vascular permeability to PEPS. DC increased the vascular permeability to PEPS but Enamine did not affect it. Findings obtained in this study may indicate that adjuvant used acts independently at the rectal mucosal membrane and at the vascular membrane for membrane for membrane permeability to PEPS.

The application of an in situ loop technique to the study of rectal absorption

The application of an in situ loop technique to the determination of rectal water flux and drug absorption in the rat is described. The procedure requires minimal surgical skill and allows rapid sampling of luminal fluid. The method was assessed by studies on: (a) the effect of sodium salicylate solutions (1% and 5% w/v) and equiosmotic solutions of mannitol (2.5% and 11.8% w/v) on rectal water flux and tissue morphology; and (b) the rectal uptake of [ 3H]prednisolone from aqueous solution. The 1% sodium salicylate and 2.5% mannitol solutions induced water movement into the lumen but caused no apparent change in the tissue morphology. The more hypertonic 5% salicylate solution and the equiosmotic mannitol solution induced water flux into the lumen and resulted in extensive cell loss. The uptake of [ 3H]prednisolone from the loop was confirmed by a simultaneous increase in plasma tritium levels.

The effects of temperature on the energetics of rectal fluid transport

Injections of fluid into the recta of isolated abdomens of the Pyrenean grasshopper Oedipoda germanica pyrenaica resulted in an immediate and sustained stimulation of oxygen consumption. The net increase in oxygen consumption was linearly related to the amount of fluid absorbed by the rectum. Rates of fluid absorption were temperature independent but the aerobic cost of fluid uptake increased 3.7-fold between 15 and 25°C. Overall rectal fluid absorption was estimated to account for 4% of the daily resting rate of oxygen consumption.

Improvement of bioavailability of poorly intestinally absorbed drugs from medium-chain glyceride base. Enhancement of the rectal absorption of cefmetazole sodium in rabbits.

Improvement of bioavailability of poorly intestinally absorbed drugs from medium-chain glyceride base. Enhancement of the rectal absorption of cefmetazole sodium in rabbits.

Lumen Perfusion of the Human Rectum In Situ: A Method to Study Mechanisms for Rectal Drug Transport in Humans

□ A lumen perfusion system was developed to study rectal transport mechanisms in humans. With this technique it is possible to perfuse a well-defined area of the rectum wall under single-pass and recirculation conditions. Sodium benzoate was used as a test drug. After absorption, sodium benzoate is conjugated with glycine to give hippuric acid which is rapidly eliminated (t1/2 = 0.5 h). Due to the short half-life it is possible to reach a steady-state concentration within 2.5 h of perfusion. Plasma concentrations of hippuric acid were determined by HPLC. The absorption influx of sodium benzoate per unit area (Φin) could be calculated using the steady-state concentration of hippuric acid during rectal perfusion, the separately measured total body clearance after intravenous injection, and a designated absorption surface of the rectum. It was shown that with this technique reproducible Φin values within one subject could be obtained. Four volunteers were perfused with four different solutions of sodium benzoate, and it was found that Φin was proportional to the four concentrations used. In the case of recirculation perfusion (two volunteers), it was found that the amount of the perfusate lost equalled the amount absorbed into the general circulation. Therefore, the possibility of major drug accumulation in the rectal lumen or mucosa could be excluded. The perfusion technique elaborated in the present study can be used to investigate the mechanism of rectal absorption in humans as well as the factors that may influence this process.

Enhancement of rectal absorption of ampicillin by sodium salicylate in rabbits.

Enhancement of rectal absorption of ampicillin by sodium salicylate in rabbits.

Promoting effect of concanavalin a on transport of sodium cefoxitin and phenol red from rat rectal compartment

Concanavalin A enhanced the rat rectal absorption of phenol red and cefoxitin at pH 7.4 and the uptake of cefoxitin into brush border membrane vesicles prepared from rat rectal membrane. The enhancing action of concanavalin A demonstrated a sodium ion dependency and was inhibited by the presence of 4,4′-diisothiocyano-2,2′-disulfonate stilbene and phlorizin. This inhibition suggests the involvement of the membrane protein fraction.

Rectal absorption of lysozyme and heparin in rabbits in the presence of non-surfactant adjuvants.

Rectal absorption of lysozyme and heparin in rabbits in the presence of non-surfactant adjuvants.

Improvement of bioavailability of poorly absorbed drugs. I. Effect of medium chain glyceride base on the rectal absorption of cefmetazole sodium in rats.

The effect of medium chain glyceride on the rectal absorption of cefmetazole sodium is investigated using an in situ experiment in rats. Each glyceride component of medium chain glyceride was separated using a high-performance liquid chromatographic method. The promoting effect of medium chain glyceride was found to be mainly due to glycerylmonocaprylate and dependent on the concentration of glycerylmonocaprylate. When cefmetazole sodium in medium chain glyceride solution was administered into the rectal lumen of rats, rapid absorption of the drug was observed leading to a residual amount of about 45% at 15 min after administration. The promoting effect of medium chain glyceride was found to be more effective in the rectum than in the small intestine.

Effect of bile salts on the rectal absorption of sodium ampicillin in rats.

Effect of bile salts on the rectal absorption of sodium ampicillin in rats.

Enhanced Rectal Absorption of Cefmetazole and Cefoxitin in the Presence of Epinephrine Metabolites in Rats and a High-Performance Liquid Chromatographic Assay for Cephamycin Antibiotics

□ 4-Hydroxy-3-methoxymandelic acid and 3,4-dihydroxy-mandelic acid were found to be potent adjuvants for the rectal absorption of water-soluble compounds in rats. Both adjuvants enhanced the absorption of two cephamycin antibiotics, cefmetazole and cefoxitin. Maximum plasma levels of the antibiotics were obtained within 30 min after rectal administration. The bioavailability of both antibiotics appeared to depend on the concentration of the adjuvant in the microenema, the dosage form used in these experiments. Instead of a microbial assay, a new chemical method involving high-performance liquid chromatography with an ion-pairing technique was developed for analyzing the cephamycin antibiotic plasma levels.

Rectal absorption of flurbiprofen, ketoprofen and indomethacin in polyacrylic acid aqueous gel preparation in rats

The bioavailability on rectal administration of flurbiprofen (FP), ketoprofen (KP) and indomethacin (Ind) with polyacrylic acid aqueous gel base was investigated in rats. When FP, KP and Ind were administered rectally with gel base at various pHs (5.0–8.0), their bioavailabilities increased upon higher pH. In the rectal administration of FP, KP and Ind with gel base at various concentrations (viscosities: 0.5–2.0 w/v%), higher bioavailabilities were obtained at lower concentrations (viscosity) of gel base. In the rectal administration of Ind with gel base containing oleic acid (10 v/v%), the bioavailability was higher and longer than that with simple gel base; however, that of FP and KP did not change without or with oleic acid. In the in vitro release experiments using micropore membrane, the effect of gel concentration (viscosity) was evident; the higher the viscosity of the gel preparation, the slower the FP, KP and Ind release. The results suggest that the release rate from the gel preparation is rate-limiting in the rectal absorption of FP, KP and Ind in gel preparations in rats. Thus, it can be assumed that polyacrylic acid aqueous gels are useful as a base for rectal administration of FP, KP and Ind.

Influence of Ionic Strength on Rectal Absorption of Gentamicin Sulfate in the Presence and Absence of Sodium Salicylate

□ The rectal absorption of gentamicin sulfate in rats, both in the presence and absence of sodium salicylate, was facilitated by the use of high ionic strength aqueous formulations. The relative order of effectiveness in promoting gentamicin absorption was sodium dihydrogen phosphate≃sodium chloride >>potassium chloride, indicating a preferential effect of sodium ions. The increased gentamicin bioavailability in response to sodium salicylate adjuvant activity appeared to be independent of and additive to the increased gentamicin absorption due to high ionic strength conditions. The inability of sorbitol to increase gentamicin bioavailability above control levels indicated that elevated osmotic pressure was not a major determinant of rectal gentamicin absorption.

Involvement of Active Sodium Transport in the Rectal Absorption of Gentamicin Sulfate in the Presence and Absence of Absorption-PromotingAdjuvants

The involvement of active sodium transport in the rectal absorption of gentamicin sulfate was examined in rats, employing aqueous microenemas of known total ionic strength (μ) in the presence or absence of absorption-promoting adjuvants. Rectal gentamicin bioavailability, which is negligible (1±1.2%) at an ionic strength of 0.15 without adjuvants, is significantly (p<0.01) increased by including adjuvants in the formulation (sodium salicylate, 12±4.0%; sodium-5-bromosalicylate, 59±15.1%; disodium ethylene(dinitrilo)tetraacetate, 24±9.3%). Pretreating the rectal mucosa cells with ouabain, a specific inhibitor of active sodium transport, significantly (p<0.01) reduced gentamicin absorption in response to all three adjuvants. In contrast to previous findings with sodium chloride, high ionic strength choline chloride (μ=1.056) did not promote gentamicin absorption. The data indicate that active sodium transport is an integral component of rectal absorption of water-soluble compounds and may be involved in the mechanism of action of absorption-promoting adjuvants.

Promoted rectal absorption of insulin: formulative parameters involved in the absorption from hydrophilic bases

The profiles of the hypoglycaemic activity of rectally-administered insulin in hydrophilic bases containing various types of polyethoxylated non-ionic surfactants as promoters was measured as a function of important parameters involved in the formulation. Relatively high surfactant concentrations were used to minimize surfactant concentration membrane dependence. Screening revealed surfactant chain-length dependencies and also high activities in sorbitan esters similar to those found in some straight chain ethers; e.g. Myrj 45, a straight chain ester, was low in activity. In the polysorbate series, a regular dependence of activity on surfactant lipophilic chain-length was found with EO 20 and EO 4, efficiency falling off on raising C from 12 to 18. Oleate was more active than stearate. In the PEG base dependence on carbon chain-length was not found for the EO 20 series but there was strong activity over the range. HLB change may be involved but is not the main factor. Insulin absorption from promoting bases was strongly affected by pH, being minimal at pH 5.2. Without promoters, however, activity was low and pH-dependence absent. A non-linear dose-dependence profile was found in the range 12–150 I.U./kg with maxima and minima in both bases, the polyacrylate base being somewhat more active than the PEG base. The insulin activity was persistently high but the positions of the maxima and minima indicated clearly that the activity and formation of insulin aggregates is a significant factor. The important parameter affecting insulin activity in rectal formulations are promoter chemical structure, pH, carrier and insulin dose-level, all of which influence the chemical as well as the biological activity.