Indomethacin Suppositories Research Articles

Rectal indomethacin for postoperative pain in orthopaedic surgery. A double-blind study

We report a double-blind study of the effectiveness of indomethacin suppositories in the relief of postoperative pain and the reduction in demand for opiate analgesia following orthopaedic procedures.

Indomethacin suppositories suppress nocturnal enuresis in children

Indomethacin suppositories suppress nocturnal enuresis in children

Use of Indomethacin Suppositories in the Prophylaxis of Recurrent Ureteral Colic

To determine the effects of indomethacin suppositories in the relief of acute colic and prevention of recurrent colic, we instituted a prospective double-blind, placebo-controlled protocol. Patients were randomized to receive either 50mg. indomethacin or placebo suppositories every 8 hours and all patients received prescriptions for supplemental narcotics to be used on an as needed basis. Relief of colic was assessed by counting the total number of supplemental narcotics used by each patient per 24 hours during the study period, which was defined as until passage of the calculus or 5 days. There were 41 patients entered into the study protocol and complete followup was available for 26. Mean calculus size was 3.4mm. in the indomethacin group versus 3.1mm. in the placebo group. All 13 patients in the control group had recurrent episodes of colic and 8 of these 13 had more than 1 recurrent episode. Five patients in the placebo group required admission to the hospital for control of pain. In contrast, only 4 of the 13 patients in the treatment group had colic and only 1 had more than 1 episode of colic. No patient in the active drug group required admission to the hospital for control of pain. Over-all the ratio of supplemental narcotic used by the placebo group versus the indomethacin group was 7.6:1 (p < 0.005). The mean interval time to passage of the calculus was slightly lower in the indomethacin group (89 versus 82 hours) but this difference was not statistically significant (p > 0.10). Our data strongly support the use of indomethacin suppositories in the prevention of recurrent colic secondary to ureteral calculi.

Indomethacin Suppository to Treat Primary Nocturnal Enuresis: Double-Blind Study

The prostaglandin synthesis inhibitor indomethacin (used as a suppository) was compared to placebo in the treatment of primary nocturnal enuresis in a double-blind crossover study. There were 12 girls and 7 boys between 6 and 15 years old. Indomethacin (50 to 100mg.) was significantly more effective than placebo in the treatment of primary enuresis. (J. Urol., 142: 1290–1292, 1989)

Comparative study of two dissolution methods for indomethacin suppositories from fatty and water-soluble bases

The continuous flow-through bead bed dissolution apparatus was compared to the rotating paddle method used by USP XXI for the dissolution testing of indomethacin suppositories. The comparison of the two dissolution techniques showed that the continuous flow-through bead bed technique is more suitable for experimental studies while the rotating paddle method is suitable for routine dissolution testing. Also, it was noted that the suppositories containing a mixture of PEG 400 and 4000 in a ratio of 5:1 presented the highest rate of drug release.

Use of indomethacin suppositories in the treatment of ureteral colic

Use of indomethacin suppositories in the treatment of ureteral colic

Indomethacin as Prophylaxis Against Ureteral Colic Following Extracorporeal Shock Wave Lithotripsy

Ureteral colic occurs in 24 to 34 per cent of all patients following extracorporeal shock wave lithotripsy. Recent research has shown prostaglandin synthetase inhibitors to be effective in relieving the pain associated with ureteral colic. Our prospective, controlled, double-blind, randomized study was designed to test the efficacy of indomethacin in the prophylactic treatment of pain after extracorporeal shock wave lithotripsy.Patients undergoing extracorporeal shock wave lithotripsy were randomized into 2 groups. Group 1 received 100mg. indomethacin suppositories twice daily and group 2 received placebo suppositories. After extracorporeal shock wave lithotripsy 2 analgesics were available to the patients: oral co-dydramol or intramuscular pethidine was offered in the normal manner by the nursing staff. The pre-extracorporeal shock wave lithotripsy x-ray was used to make a quantitative estimate of the total stone burden in each patient. The post-extracorporeal shock wave lithotripsy analgesic requirement was used to compare the 2 groups.Of 112 patients recruited to the study 55 received indomethacin and 57 received placebo. The request for analgesia in the 2 groups was not different (28 of 55 and 33 of 57, respectively). However, in the indomethacin group only 6 patients required pethidine (10 doses), compared to 18 (41 doses) in the placebo group. This difference is statistically significant (p less than 0.01). There was no difference between the 2 groups in the occurrence of ureteral steinstrasse.Indomethacin has been shown to be effective in the prophylactic treatment of ureteral colic after lithotripsy.

Evaluation of polyvinyl alcohol hydrogel as a sustained-release vehicle for rectal administration of indomethacin.

In order to evaluate an indomethacin polyvinyl alcohol (PVA) hydrogel for rectal administration, the in vitro release characteristics of indomethacin from the hydrogel and indomethacin plasma concentrations after rectal administration were examined. The PVA hydrogel containing indomethacin was prepared by a low-temperature crystallization method. The release of indomethacin from the PVA hydrogel agreed with the Fickian diffusion model for 10 hr. Rectal administration of indomethacin hydrogels to rats yielded high indomethacin plasma concentrations, without producing a sharp peak, and a sustained-release effect. In dogs, the indomethacin hydrogel produced a similar sustained-release effect; however, the indomethacin plasma concentration was relatively low compared with that of an indomethacin suppository.

Indomethacin Suppositories are Effective and Well Tolerated

Indomethacin Suppositories are Effective and Well Tolerated

Effectiveness of indomethacin (indocid) suppositories as post-episiotomy analgesia

A double-blind, randomised placebo-controlled study was carried out to assess the efficacy of indometacin suppositories as a post-episiotomy analgesic. Thirty patients received 2 × 100 mg indometacin suppositories, and 30 patients received placebo suppositories within 15 min of an episiotomy repair operation. Local infiltration of the episiotomy incision was performed using 20 ml of 0.5% lignocaine in every case. Subjective symptoms of pain were evaluated 15, 30, 60 and 90 min post-episiotomy repair. Average numbers of hours as lying in patients after delivery is 4 h. None of the patients who received indometacin complained of post-episiotomy pain; whereas the patients on placebo manifested varying degrees of pain.

Comparison of serum indomethacin profiles after rectal administration of two brands of indomethacin suppositories in healthy volunteer subjects

Previous in vitro dissolution data indicated a much slower release of indomethacin from Indocid suppositories than from Imbrilon suppositories; both products contain 100 mg of indomethacin. Since in vitro findings require in vivo validation before clinical recommendations can be made, the present study was designed to compare the in vivo release characteristics of the two products. The study was carried out in 12 volunteer subjects in a fully randomized double-blind cross-over fashion and involved administration of Indocid and Imbrilon suppositories at bedtime. Venous blood samples were obtained over the first 12 h post-drug administration, while pooled urine was collected from 0–12 and 12–24 h. Indomethacin content of all samples were measured using HPLC. The experimental data were compared using the following parameters: T max, C pmax and all other timed plasma concentrations, AUC 0–12h and cumulative urinary excretion data from 0–12, 12–24 and 0–24 h. Statistical analyses, using the paired t-test, indicated that no statistically significant differences ( P > 0.05) occurred between any of the measured parameters for the two products. It is therefore unlikely that clinically significant differences between the two products will be seen during treatment in patients.

Indomethacin Suppositories

To the Editor: —Indomethacin suppositories are well known to produce rectal ulceration and bleeding.1,2 However, we are not aware of any reports of fistula formation. An 84-year-old woman presented to the Flinders Medical Centre with a three-week history of pain and discharge in the vulval region. She had a five-year history of rheumatoid arthritis and had used indomethacin suppositories nightly. She continued to insert the suppository up until the time of admission. There had been no history of rectal bleeding. There was a history of fecal soiling but no diarrhea. Examination of the perineum revealed a 1.5-cm elliptical ulcer on the posterior aspect of the (r) vulva. Subsequent examination under anesthesia revealed that the vulval ulcer connected with the lower rectum. Biopsy of the ulcer and rectum showed chronic inflammatory changes. Subsequent treatment of sitz baths, cathartics, and adequate analgesia resulted in healing of the vulval side of the fistula in four weeks. However, sigmoidoscopy performed at 20 weeks showed evidence of continuing granulation tissue in the rectum suggesting that the fistula has not yet completely healed. Local rectal irritation, mucosal inflammation, and necrosis with profuse bleeding can occur after the use of indomethacin suppositories. Fistula formation occurred in this case most likely because of continued use despite severe perineal pain. Elderly patients are well known for their stoicism and inflexibility toward taking of drugs despite the presence of side effects. This previously unreported side effect is a further example of a rigid behavior pattern toward medication in the elderly.

Prostaglandin synthetase inhibition with indomethacin rectal suppositories in the treatment of acute and chronic urinary calculus obstruction.

The effect of indomethacin suppositories on both acute urinary colic and urinary calculus, resistant or refractory to conventional therapy with analgesics and spasmolytics was investigated. Fifty-five patients with acute urinary colic refractory to treatment with repeated injections of antispasmodics and analgesics had dramatic or complete pain relief after receiving indomethacin suppositories (100 mg) (P less than 0.01). Fifteen of the 55 patients passed urinary stones within 30 days of treatment with indomethacin. Three out of 30 other patients with renal or ureteric stones were treated with indomethacin suppositories (100 mg) twice daily. Twenty-one of the 30 patients passed their stones within 30 days of treatment. It is concluded that indomethacin suppositories can relieve acute urinary colic resistant to treatment with analgesic/antispasmodic drugs, and facilitate expulsion of urinary calculi. The mechanism of action of indomethacin is discussed in terms of its analgesic and anti-inflammatory effects and its prostaglandin synthesis inhibition.

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

The suggestion that the intestinal mucosa may be abnormally permeable and thus a site of antigen absorption in rheumatoid arthritis was tested by a 51Cr EDTA intestinal permeability test. Twelve patients with rheumatoid arthritis untreated by non-steroidal anti-inflammatory drugs (NSAIDs) had normal test results, while 12 NSAID-treated patients had increased intestinal permeability. Ten volunteers ingested aspirin, ibuprofen and indomethacin 8 and 1 hours before the study. The increased intestinal permeability was proportional to drug potency to inhibit cyclo-oxygenase. Intestinal permeability also increased following an indomethacin suppository, which suggests that the effect is systemically mediated. 111Indium leucocyte scintigrams and faecal collection showed no evidence of intestinal inflammation in 9 patients untreated by NSAIDs. Twenty-nine of 53 NSAID-treated patients showed abnormal localisation of 111indium in the right iliac fossa at 20 hours, and 32 of 49 patients had increased faecal excretion of 111indium. A 99mTc-porphyrin scan suggested that the main site of NSAID-induced intestinal inflammation was the small bowel. NSAIDs are thus shown to disrupt intestinal integrity and long term treatment leads to inflammation of the small intestine.

Antipyretic effect of indomethacin suppository in rabbits.

We have designed a thermistor rectal probe thermometer for measuring the antipyretic activity of suppositories. Using this thermistor probe, we tested the antipyretic effect of an indomethacin suppository in comparison with oral and intravenous administrations in rabbits (male, 2.5-2.9 kg). The rectal temperature of normal rabbits remained unchanged after rectal and intravenous administration of indomethacin, 25 mg/body and 10 mg/kg, respectively. The antipyretic effect was tested in febrile rabbits injected with bacterial pyrogen, lipopolysaccharide (LPS) 0.2 microgram/kg (i.v.). The dose-dependent antipyretic activities were observed in febrile rabbits administered with indomethacin by rectal (6.3-23.7 mg/body), intravenous (2.5-10 mg/kg) and oral (2.5-20 mg/kg) routes. When indomethacin was administered simultaneously or 1 h after LPS, the most potent antipyretic effect was observed in the case of rectal administration and the weakest effect was observed in that of oral administration. These data indicate that the rectal administration of drugs can produce a potent antipyretic activity, not inferior to that of the intravenous injection.

Prostaglandins mediate postoperative pain in Falope ring sterilization

To test the hypothesis that prostaglandins mediate the high incidence of postoperative pain in patients undergoing mechanical tubal occlusion, we studied the effect of premedication with a prostaglandin synthetase inhibitor in patients having Falope ring sterilization. Fifty-two women were randomly divided into two groups in which 19 (study group) received a preoperative indomethacin rectal suppository (100 mg) while 33 (control group) received nothing. Postoperative narcotic analgesics were administered as required, and for persistent pain an indomethacin suppository was given in the recovery room. Twenty-four percent of the control group required a postoperative indomethacin suppository because of persisting pain compared to none of the study group (p < 0.02). These results suggest that prostaglandins mediate, and premedication with a prostaglandin synthetase inhibitor may lessen, postoperative pain in patients having Falope ring sterilization.

Management of polyuria subsequent to pituitary surgery based on the diurnal pattern of urinary excretion

Polyuria subsequent to pituitary surgery was studied in 64 cases. Most cases of postoperative polyuria were due to diabetes insipidus. These cases showed a triphasic pattern in daily urinary volume. Observation of hourly urinary volume in polyuria revealed four diurnal patterns of urinary excretion: rhythmic, continuous, transient, and unspecific. Clinical observation of diurnal patterns has an advantage, in terms of simplicity of procedure, in immediately determining the nature of the polyuria, prognosticating diabetes insipidus, and eliminating inappropriate procedures in treatment. Indomethacin suppository is considered to be a favorable agent in reducing polyuria without disturbing the diurnal pattern in diabetes insipidus

Indomethacin Treatment of Acute Pancreatitis: A Controlled Double-Blind Trial

Thirty patients with acute pancreatitis were allocated to indomethacin suppositories, 50 mg twice daily, or identical-looking placebo suppositories for 7 days in a controlled double-blind trial. The groups of patients were not different with regard to age, sex, etiology, or number of Ranson criteria. The number of days with pain and number of opiate injections were significantly less in patients treated with indomethacin. The median values of serum amylase and serum calcium were not different before or at any day during treatment. Bleeding from the gastrointestinal tract was not seen.

Are prostaglandins cytoprotective in the human large intestine? The effect of indomethacin on rectal mucosal function and prostaglandin E2 release in vivo.

To test the hypothesis that prostaglandins are cytoprotective in the human large intestine, we investigated the effect of withdrawal of treatment with indomethacin suppositories on bowel habit and on rectal mucosal electrolyte transport and prostaglandin production in 8 patients taking such treatment for rheumatological disorders. Discontinuation of indomethacin doubled rectal mucosal prostaglandin E2 release (p less than 0.05) measured by in vivo rectal dialysis. Although there was no significant overall change in stool frequency, stool consistency, rectal bleeding or sodium absorption (also assessed by rectal dialysis), sigmoidoscopic appearance (p = 0.05), rectal mucosal potential difference (p less than 0.05) and potassium transport (p = 0.01) each reverted towards normal on indomethacin withdrawal. These results accord with the theory that, as in the upper gastrointestinal tract, prostaglandins may play a role in the maintenance of rectal mucosal structure and function.

The comparison of a novel continuous-flow dissolution apparatus for suppositories with the rotating basket technique

The dissolution rate of a drug from a solid dosage unit is an important parameter affecting drug bioavailability. Whjile dissolution testing has received much attention in the cases of tablets and capsules, it has received much less attention with suppositories. It was for this reason that the performance of a novel flow-through bead-bed apparatus was assessed in our laboratories. A flow-through dissolution chamber based on a published American design was constructed. It was tested in two ways: firstly using fatty based benzocaine suppositories, dissolution rates were determined at different temperatures. The data obtained agreed well with original published data indicating that the apparatus can be easily fashioned from standard laboratory equipaient and can give reproducible results in different laboratories. For comparison the benzocaine suppositories were also tested using a rotating basket method. Similar dissolution profiles Were obtained using the two methods at 37°C. Secondly the dissolution profiles of two commercially available indomethacin suppositories were measured using both the flow-through bead-bed apparatus and the more established rotating basket method. Although both products contained the same dose of indomethacin in a polyethylene glycol base, clear differences were noted between the dissolution profiles of the two products. The difference, however, was much more marked when using the flow-through bead-bed apparatus. These data therefore indicate that the latter technique may be a more precise tool for monitoring the effects of subtle formulation changes on dissolution profiles. In the case of indomethacin, from a pharmacological standpoint, a slower release rate is advantageous as such a product is likely to be more effective at relieving early morning stiffness after an evening dose.