Rectal Membrane Research Articles

Effect of Salicylate on the Rectal Absorption of Lidocaine, Levodopa, and Cefmetazole in Rats

Salicylic acid and sodium salicylate have been found to enhance the absorption of lidocaine, levodopa, and cefmetazole after rectal administration to rats. These drugs represent a base (lidocaine), an acid (cefmetazole), and a substance (levodopa) which exists as a zwitterion in solution. The rectal absorption of each type of drug, as well as theophylline, a neutral compound, was enhanced by salicylate, particularly at pH values where the substances exist primarily in their ionic form. A requirement for the observed enhancement is that salicylate be present in the rectal membrane. The loss of drug from the perfusing solution was greater from solutions having an ionic strength of 0.75 than from those with μ = 0.15.

Enhanced Rectal Absorption of Theophylline, Lidocaine, Cefmetazole, and Levodopa by Several Adjuvants

Ten potential adjuvants for rectal absorption which are structurally similar to salicylate have been examined using an in situ perfusion of the rat rectum technique as well as an in vivo absorption method from microenemas. All of the adjuvants studied readily disappeared from the perfusate at pH 4.5; however, several were not absorbed well at pH 7.4. Only those that were lost rapidly from the perfusate at pH 7.4 were effective in enhancing the disappearance of the drugs (theophylline, lidocaine, cefmetazole, and levodopa) at either a pH of 4.5 or 7.4. The compounds that were effective in promoting the disappearance of drugs from the rectal perfusate all had hydroxy and carboxy groups. Those substances lacking a hydroxy group were not effective. The binding of these potential adjuvants and salicylates to rat rectum tissue was studied by equilibrium dialysis. Those adjuvants with relatively high binding to rat rectal tissue were better absorbed themselves and promoted the disappearance of drugs more than those substances exhibiting little binding. Thus, adjuvant binding to some feature of the rectal membrane appears to be important in the enhanced absorption of drugs from the rectum under the conditions of this study.

Effects of Aminophylline Suppositories Prepared in Hospital Pharmacy on the Rectal Membrane

Effects of Witepsol base, P. E. G. base and aminophylline suppositories (Witepsol base, P. E. G. base) on the rectal mucous membrane in rabbits were investigated. These suppositories were administered once in a single dose or once a day for 2 weeks. The rectum extirpated 6 hrs after last insertion was examined with unaided eyes and optical and scanning electron microscopes. As a result, no damage by aminophylline suppositories and bases was observed, and irritative effect of Witepsol base was in about the same degree as that of P. E. G. base.

Influence of surfactants, polymers, and concentration of the water phase on in vitro drug release from emulsion-type suppositories.

Generally, drug release from the base is considered to be one of the most important parameters in evaluating the pharmaceutical usefulness of suppositories in vivo and in vitro. In spite of the therapeutic importance and wide applications of suppositories, the absorption mechanisms and the factors determining their absorption characteristics have not been established. The present study was undertaken to investigate the effects of surfactants, polymers, and concentration of the water phase on in vitro drug release emulsion-type suppositories. N1-(2'-furanidyl)-5-fluorouracil (FT-207), theophylline and indomethacin were chosen as model compounds. In order to clarify the behavior of the rectal membrane, the following three different methods for studying drug release (in vitro) were selected : (1) the filter membrane technique, (2) the use of membranes of animal origin, (3) in situ rectal recirculation technique. The following results were obtained. (1) In the case of readily water-soluble compounds such as FT-207, the amount of drug released increased with increase of the water content in the suppository base. (2) On the other hand, no significant effect of concentration of the water phase in the suppository base was found for fatty drugs such as indomethacin. (3) By the addition of aqueous polymer, the amount of drug released could be controlled and the release prolonged in the emulsion-type suppository base.

Rectal delivery of antiinflammatory drugs. I. The influence of antiinflammatory drugs on rectal absorption of beta-lactam antibiotics.

The effects of non-steroid antiinflammatory (NSAI) drugs on the rectal membrane were studied by measuring the change in the rectal absorption of ampicillin and cephalothin. All the NSAI drugs studied were found to case a remarkable enhancement of the rectal absorption of antibiotics which were not able to permeate readily through the rectal membrane in the absence of NSAI drugs. The optimum concentrations of NSAI drugs as adjuvants in triglyceride suppositories containing 10% ampicillin sodium were 1.5% for indomethacin sodium and diclofenac sodium, 5% for mepirizole, 7.5% for phenylbutazone, and 10% for sodium salicylate. These concentrations of NSAI drugs were used in a study of the promoting efficacy of the drugs as adjuvants for the rectal absorption of antibiotics. The promoting effects of adjuvants in dogs were inferior to those in rabbits. From simultaneous measurements of NSAI drugs and antibiotic, it was found that the absorption of antibiotic started at the early stages after the administration of suppositories and the peak blood level was reached while the blood concentration of NSAI drug was still increasing. From these results, it was suggested that the NSAI drugs made the mucosal barrier leaky to water-soluble antibiotics at the early stages of permeation of the NSAI drugs through the rectal membrane, and that the barrier rapidly recovered its normal properties even while the permeation of NSAI drug was continuing and a considerable amount of antibiotic still remained in the rectal cavity. Alinear correlation between the enhanced absorption of antibiotics and the antiinflammatory activity of NSAI drugs against carrageenan-induced edema was observed.

Studies on absorption promoters for rectal delivery preparations. I. Promoting efficacy of enamine derivatives of amino acids for the rectal absorption of beta-lactam antibiotics in rabbits.

Enamine derivatives of amino acids were synthesized and their promoting efficacies for the rectal absorption of β-lactam antibiotics were studied in rabbits. Ethyl acetoacetate (EtAA) enamine derivatives were preferentially studied because of the low toxicity of EtAA generated by the hydrolysis of the enamine moiety in the rectum and blood stream. The EtAA enamine of sodium D-phenylglycine (PG EtAA Na) was found to have remarkable promoting efficacy for the rectal absorption of sodium ampicillin, cephalothin, cephapirin, cefazolin and cephaloridine. Other enamine derivatives of amino acids also showed promoting efficacy for the rectal absorption of penicillins and cephalosporins which could not permeate alone due to their poor lipid affinity. The promoting efficacy of PG EtAA Na for the rectal absorption of antibiotics increased with decrease in their partition coefficients. The present results suggest that the enamine derivatives of amino acids are clinically applicable for use in rectal delivery preparations of penicillins and cephalosporins which cannot permeate unaided through the rectal membrane.

Application of Duhamel's operation for the surgical treatment of rectal cancer.

Several sphincter-preserving procedures for surgical removal of cancer at the upper or middle part of the rectum often cause disturbances of the ano-rectal and bladder functions. To preserve these functions it is important to minimize the damage to the anal sphincter as well as to the pervic nerves and to preserve the rectal mucous membrane as much as possible. Duhamel's procedure was employed with very satisfactory results.

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.

URINARY INCONTINENCE IN THE FEMALE

The record of attempts to cure urinary incontinence in the female is an interesting illustration of the inability of most men to go straight to the point in working on any problem involving a part of the human body. The real importance of the condition, in its possibilities of discomfort and even disability to the individual, is well shown by the long array of procedures which have been advocated to help this distressing trouble. Until a few years ago, no satisfactory method of cure for incontinence in the female was known; all of the methods were more or less futile, many of them ridiculous, and some of them even dangerous. Contractile collodion has been painted over the meatus. Radial cauterization, as in a redundant rectal mucous membrane, has been used. Paraffin has been injected under the mucous membrane to make a permanent pressure against the canal. A sterile silk suture