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PubMed1990

Indomethacin sustained-release suppositories containing sugar ester.

We prepared indomethacin (IM) sustained-release suppositories using sugar ester (SE) as an additive. The suppositories were prepared by the fusion method with IM, SE, and Witepsol H-15 (H-15) and their availabilities in vitro and in vivo were evaluated mainly by the drug release test and the absorption test in rabbits, respectively. The softening point of the suppositories increased with increasing SE content. In the release test with the Muranishi method, slow-release profiles were obtained when the SE content was more than 52.5%. The absorption of IM from these suppositories, however, was very little. In the other release test, e.g. immersion method with gauze, all of the suppositories with SE showed slow-release profiles, and the drug release rates clearly depended on the SE content. The drug was released from the suppositories by the following leaching-type mechanism proposed by Higuchi. The suppository with a 30% SE content showed a sustained-plasma level of IM, but the other suppositories did not. It was concluded that an appropriate content of SE (i.e. 30%) in the suppository base was required to obtain sustained-release because it reasonably regulated the infiltration of rectal fluid into the suppository and the mechanical strength of the suppository against disintegration.

Animals↗
PubMed1997

[Sustained release double-layered progesterone suppository for luteal support therapy].

A sustained release suppository containing progesterone with a double-layered structure was prepared for the treatment of the luteal phase defect. Hydroxypropylcellulose-H (HPC) and Carbopol-934P (CP) were used as bases of the inner layer and Witepsol W35 was used as a base of the outer layer. The strength of the inner layer (stick) decreased with the increase of the rate of content of HPC component. The strength of the stick which was prepared from a mixture of HPC and CP in a ratio of 1:1, was inverse by proportional to the rate of the addition of crystalline cellulose (CC) and the amount of released drug was proportional to the rate of the addition of CC. The area under the drug release curve of the stick containing 60% of CC in the base was about 12 times of the stick containing no CC (control stick). Furthermore, the mean release time of the stick containing 60% of CC became about a half of the control stick. It was suggested that the drug release of progesterone from the stick could be controlled by changing the rate of the addition of CC. Two types of suppository which containing progesterone in both phases (suppository A) and in the stick alone (suppository B) were prepared. Both suppositories showed a sustained release property and suppository B had a lag time of two hours. When the suppositories were administered in to the vagina of rabbits, they showed a sustained release property and a rapid rise in the serum concentration was more suppressed than an ordinary Witepsol suppository. One hour after the administration of the two layered suppository, some parts of the suppository was identified macroscopically to be remained in the vagina. The usefulness of the double-layered suppository as a hospital preparation should be suggested after the attainment of the optimization of the formulation.

Acrylic Resins↗
PubMed1992

Pharmaceutical characterization of corticosteroid suppository treatment for ulcerative colitis.

The dose and method of administration of a corticosteroid given for the treatment of patients with ulcerative colitis are determined according to the range of the diseased area and its severity. In this study, we prepared a hydrophilic suppository consisting of water-soluble prednisolone sodium succinate (PSL-SS) and a hydrophilic base, polyethylene glycol (PEG), and a hydrophobic suppository consisting of water-insoluble prednisolone (PSL) and a hydrophobic base, Witepsol (WT). We determined the spread of the drugs after intrarectal administration and their therapeutic effect. When rats received the hydrophilic suppository, the drug spread farther oral than when they received the hydrophobic suppository. Moreover, more than half of the PSL-SS recovered was observed to have changed into PSL. A therapeutic effect on the colitis induced in rats by acetic acid was noted in the area up to 10 cm from the anus in the case of the hydrophilic suppository, while the effect of the hydrophobic suppository was seen only in the area up to 2.5 cm from the anus. In patients with ulcerative colitis, the hydrophilic suppository showed retrograde spread to a site 34.4 +/- 5.3 cm from the anus, while the hydrophobic suppository spread to a site 19.0 +/- 2.4 cm from the anus. These results suggest that a hydrophobic suppository should be used for patients in whom inflammation is confined to the rectum, and a hydrophilic suppository used for patients in whom inflammation reaches the rectum and the middle part of the sigmoid colon.

Administration, Oral↗
PubMed2006

Reciprocating dialysis tube method: periodic tapping improved in vitro release/dissolution testing of suppositories.

The reciprocating dialysis tube (RDT) method can be used for in vitro release/dissolution testing of suppositories and has been reported to show good in vitro and in vivo correlation. However, for suppositories with viscous excipients, the result remains variable and generally under-predicts in vivo absorption. The purpose of this study was to assess whether periodic tapping of the closure of the RDT could improve in vitro release testing of suppositories. Two commercially available acetaminophen suppositories (A and B) that showed characteristic release behavior under normal rectal temperatures (37 and 38 degrees C) were chosen as test suppositories. In the absence of tapping, suppository A showed different release profiles at 37 and 38 degrees C, but the difference disappeared with periodic tapping. This finding was consistent with minimum temperature effect in the rectal absorption of suppository A in rabbits. Suppository B showed distinct release profiles at 37 and 38 degrees C irrespective of tapping, and the rectal absorption of suppository B in rabbits was affected by temperature. The test variability (CV% and ranges of release values) was substantially reduced in the presence of tapping. In conclusion, the addition of periodic tapping to RDT method developed in this study could improve in vitro release testing of suppositories.

Acetaminophen↗
PubMed1998

Polyethylene glycol versus vegetable oil based bisacodyl suppositories to initiate side-lying bowel care: a clinical trial in persons with spinal cord injury.

INTRODUCTION: Neurogenic bowel dysfunction resulting from spinal cord injury (SCI) frequently requires bowel care (BC) with stimulant suppositories for initiation of effective defecation. The excessive time required for BC and bowel complications have limited quality of life after SCI. OBJECTIVE: To test the hypothesis that: the time required for bowel care with bisacodyl suppositories can be reduced by substituting a polyethylene glycol base (PGB) for the traditional hydrogenated vegetable oil base (HVB) in the suppository. SETTING: Inpatient SCI medicine unit. SUBJECTS: Fourteen persons with SCI with chronic stable paralysis from upper motor neuron SCI for greater than one year with a stable HVB bisacodyl suppository initiated BC. DESIGN: Crossover Controlled. METHOD: Subjects received HVB bisacodyl suppositories for six sequential BC sessions and then were crossed over to PGB bisacodyl suppositories for six more BCs. OUTCOME MEASURES: BC event times were utilized to derive BC intervals: suppository insertion to first flatus= Time to flatus, first flatus until the beginning of stool flow = Flatus to stool flow, begin stool flow until end stool flow = Defecation period, end stool flow until end of clean up = Clean up, and suppository insertion until end clean up = Total bowel care time. RESULTS: The data included two groups of BC sessions: HVB (n = 84) and PGB (n = 81). Mean times in minutes and P values from t tests for paired samples yielded: Time to flatus: (HVB 31, PGB 12.8 P < 0.002), Defecation period: (HVB 58, PGB 32, P < 0.0005), Clean up: (HVB 1.9, PGB 3.2 P = 0.165), Total bowel care time: (HVB 102, PGB 51.2 P < 0.0005). CONCLUSION: This analysis suggests that PGB based bisacodyl suppositories may stimulate reflex defecation sooner and shorten the Total BC Time as compared with HVB bisacodyl suppositories.

Bisacodyl↗
PubMed1997

Comparison of mesalazine suppositories in proctitis and distal proctosigmoiditis.

BACKGROUND: Mesalazine suppositories at 500 mg b.d. are a safe and effective treatment for patients with ulcerative proctitis or distal proctosigmoiditis. Recently a mesalazine 1 g suppository (Pentasa) has been developed. METHODS: Fifty patients with active ulcerative colitis extending not beyond 20 cm from the anus on sigmoidoscopy, participated in a randomized single-blind study comparing the efficacy, tolerance and acceptance of the new Pentasa mesalazine 1 g suppository, given once daily versus Claversal mesalazine 500 mg suppository b.d. RESULTS: After 2 weeks, clinical remission was observed in 16 of 25 (64%) in the Pentasa group and in 7 of 25 (28%) in the Claversal 500 mg b.d. treated group; sigmoidoscopic remission occurred in 13 of 25 (52%) in the Pentasa group and in six of 25 (24%) in the Claversal group (P < 0.01). After 4 weeks, clinical and sigmoidoscopic remission were observed, respectively, in 84 and 76% of patients treated with Pentasa suppositories, and in 80 and 72% of patients treated with Claversal suppositories 500 mg b.d. (P = N.S.). The patients' evaluation for tolerability and practicality showed that the Pentasa suppository was significantly superior to the Claversal suppository. CONCLUSIONS: Pentasa 1 g suppository once daily induces a quicker clinical and sigmoidoscopic remission, and was better tolerated, than the Claversal 500 mg suppository b.d., and it may represent an advance for the topical treatment of distal proctosigmoiditis.

Adult↗
PubMed2005

Lidocaine suppositories for prostate biopsy.

OBJECTIVES: To evaluate, in a randomized prospective study, the efficiency of transrectal lidocaine suppositories to reduce pain during transrectal prostate biopsy, as suppositories allow longer for the agent to be effective. PATIENTS AND METHODS: In all, 100 patients were randomized to receive either a placebo suppository or 10 mL of 2% (200 mg) lidocaine gel rectally 10 min before biopsy, or a suppository containing 60 mg lidocaine 1 or 2 h before biopsy. Costs (in euros) per application were 0.82 for gel and 0.63 for suppositories. In all patients the same 10-core biopsy technique was used. Pain was evaluated using a visual linear pain scale ranging from 0 to 100 points; the patient's side of the scale did not show the number of points. RESULTS: The mean pain scores in the placebo, lidocaine gel, and lidocaine suppositories applied 1 h and 2 h before biopsy were 36.2, 40.9, 29.2 and 21.2, respectively. Thus patients with no anaesthesia reported 25% more pain than those receiving lidocaine suppositories 1 h before and 71% more pain than those receiving lidocaine suppositories 2 h before biopsy (P = 0.002). CONCLUSIONS: Lidocaine suppositories at a lower dose and with longer to take effect can be used to reduce pain significantly more effectively than the commonly used gel. As suppositories are easy to use and cheap, they are recommended in daily routine prostate biopsy.

Adult↗
PubMed1993

Bioavailability and diuretic effect of bumetanide following rectal administration of suppositories containing weak acids in human subjects.

The bioavailability of bumetanide following the oral administration of tablets, or the rectal administration of either macrogol suppositories or suppositories with and without weak acids were evaluated in human subjects. The absorption of bumetanide from those suppositories containing bumetanide without weak acids (control suppositories) was extremely poor, while the absorption from those suppositories containing citric acid or tartaric acid was enhanced. The mean area under the plasma concentration-time curve (AUC) following the rectal administration of the suppositories containing citric acid and tartaric acid was 52 and 62%, respectively, of that following the oral administration. On the other hand, the absorption rate constant (ka) and the mean residence time (MRT) following the rectal administration of the suppositories containing weak acids increased significantly compared to those administered orally. The time (Tmax) required to achieve the maximum plasma concentration (Cmax) in the plasma following the rectal administration of the suppositories containing weak acids was significantly shortened compared to the time of those administered orally. These results indicated that the bumetanide contained in the suppositories containing weak acids might be absorbed rapidly after administration. The diuretic effect of bumetanide following the oral and rectal administration was also evaluated. Sufficient diuretic effects were obtained following the rectal administration of the suppositories containing weak acids.

Administration, Oral↗
PubMed2005

Design of controlled-release morphine suppositories containing polyglycerol ester of fatty acid.

Controlled-release morphine suppositories were prepared by utilizing polyglycerol ester of fatty acid (PGEF). The addition of PGEF to fatty suppository base Witepsol H15 resulted in a decrease of morphine release rate from suppositories. Among PGEFs examined, decaglycerol heptabehenate (HB750) was the most effective additive for the controlled-release of morphine from fatty suppositories. The apparent viscosity of suppository bases increased with the increase in HB750 content, and good correlation was observed between the apparent viscosity of suppository bases at 37 degrees C and the amount of HB750 added in the mixed base. The in vitro release rate of morphine was decreased by the addition of HB750 and the release rate constant (Higuchi's rate constant) for morphine release was significantly correlated with the HB750 content in the mixed bases as well as the apparent viscosity of mixed bases, indicating that the release of morphine from the mixed bases could be regulated by the HB750 content in the mixed bases. After rectal administration of Witepsol H-15-HB750 mixed suppositories to dogs, plasma concentrations of morphine did not increase rapidly at early time periods, but relatively high levels of morphine in plasma were sustained for longer time periods. Mean residence time of morphine was considerably prolonged without changing relative bioavailability in the case of the mixed base suppositories containing 15-17% HB750, compared with the Witepsol H15 suppository, clearly indicating that the mixed bases containing HB750 are expected to be useful for the design of controlled-release morphine suppositories.

Analgesics, Opioid↗
PubMedDate not supplied

Patient attitudes to perioperative suppository administration for postoperative analgesia.

Four hundred surgical patients were questioned preoperatively to ascertain their attitudes to suppository analgesia. Given a choice, 82 per cent of patients expressed a preference for intramuscular administration of diclofenac, with 18 per cent choosing a suppository. Males were more likely than females to choose an intramuscular injection. Males choosing a suppository were more likely to belong to a higher socio-economic group while females choosing a suppository were more likely to be married. Twenty-three per cent of patients who initially opted for intramuscular administration changed to suppository administration when the possibility of pain or discomfort at the injection site was explained. Females who changed to suppository administration were more likely to belong to a higher socio-economic group and to be married. Twenty-seven per cent of patients choosing an intramuscular injection expressed concern if a suppository were to be inserted without consent. Eleven per cent of patients choosing a suppository expressed similar concern. There is an overall reluctance, particularly within the male population to accept suppository analgesia. Patients from higher socio-economic groups may be more willing to accept what they perceive to be less traditional forms of treatment.

Analgesia↗
PubMed2003

Physicochemical characterization and in vivo evaluation of thermosensitive diclofenac liquid suppository.

Liquid suppository systems composed of poloxamers and bioadhesive polymers were easy to administer to the anus and mucoadhesive to the rectal tissues without leakage after the dose. However, a liquid suppository containing diclofenac sodium could not be developed using bioadhesive polymers, since the drug was precipitated in this preparation. To develop a liquid suppository system using sodium chloride instead of bioadhesive polymers, the physicochemical properties such as gelation temperature, gel strength and bioadhesive force of various formulations composed of diclofenac sodium, poloxamers and sodium chloride were investigated. Furthermore, the pharmacokinetic study of diclofenac sodium delivered by the liquid suppository was performed. Diclofenac sodium significantly increased the gelation temperature and weakened the gel strength and bioadhesive force, while sodium chloride did the opposite. The liquid suppositories with less than 1.0% of sodium chloride, in which the drug was not precipitated, were inserted into the rectum without difficulty and leakage. Furthermore, liquid suppository gave significantly higher initial plasma concentrations and faster Tmax of diclofenac sodium than did solid suppository, indicating that drug from liquid suppository could be absorbed faster than that from solid one in rats. Our results suggested that a thermosensitive liquid suppository system with sodium chloride and poloxamers was a more physically stable, convenient and effective rectal dosage form for diclofenac sodium.

Adhesiveness↗
PubMed2004

Development of suppository formulation safely improving rectal absorption of rebamipide, a poorly absorbable drug, by utilizing sodium laurate and taurine.

To develop the safe formulation that can safely improve bioavailability of poorly absorbable drugs and that is practically available, we prepared the suppositories of rebamipide, a poorly soluble and poorly absorbable antiulcer drug, by employing the combinatorial use of sodium laurate (C12), an absorption enhancer, with taurine (Tau) or L-glutamine (L-Gln), an adjuvant exerting the cytoprotective action. Although the dissolution of rebamipide from fatty base (FB) suppository prepared using Witepsol H-15 was very slow, it was remarkably improved by the addition of C12 and L-Gln or Tau into the suppository. On the other hand, the dissolution of rebamipide from water-soluble base (WB) suppository prepared using polyethylene glycol was very rapid and the addition of adjuvants did not influence its dissolution so much. Rectal absorption of rebamipide examined in rats was remarkably improved by FB suppository containing C12 or both C12 and Tau, while the enhancing effect of C12 was relatively small in the case of WB suppositories. Biochemical and histopathological studies have confirmed that FB suppository containing both C12 and Tau or L-Gln did not cause any serious local damage, while FB suppository containing C12 only caused the erosion and shrinkage for a lot of rectal epithelial cells. In conclusion, FB suppository employing the combinatorial use of C12 with Tau could be a promising formulation that is effective and safe enough for poorly absorbable drugs to be practically administered.

Alanine↗
PubMed2001

Evaluation of an acetic acid ester of monoglyceride as a suppository base with unique properties.

The objective of this investigation was to evaluate an acetic acid ester of monoglycerides made from edible, fully hydrogenated palm oil (AC-70) as a suppository base and compare it with a commercially available semisynthetic base (Suppocire AI). Benzocaine and miconazole were used as model drugs. Suppositories were prepared by the fusion method. The drug loads in the suppositories were kept at 2% to 5% (wt/wt). In vitro release of drug from the suppositories into Sorensen's phosphate buffer (pH 7.4) was studied using a US Pharmacopeia dissolution apparatus 1 and a spectrophotometer. The melting behavior of the bases and the physical state of the drug in the suppositories were studied using a differential scanning calorimeter (DSC). Powder x-ray diffractometry was used to study any possible polymorphic changes in the AC-70 base during formulation and storage. In vitro release studies revealed that the release of benzocaine from the AC-70 suppository was substantially slower than that of the commercial AI base. At a 2.5% (wt/wt) benzocaine load, the release of drug from the AC-70 suppositories was found to be linear. This slow and linear release was attributed to the physical property of the base, which forms liquid crystalline phases in the aqueous dissolution medium. The lyotropic liquid crystalline phase has the ability to incorporate drug into its structure and can control the release kinetics of the drug from such a system. The apparent pH of the release medium (water) was decreased by 1 to 1.5 pH units when the AC-70 base was used. The DSC studies revealed that the melting range of the AC-70 base is 36 degrees C to 38 degrees C, which is ideal for suppository formulations. The results of these studies support the possibility of using this new base for slow-release suppository formulations. This base may be of particular interest for a drug that requires an acidic environment to maintain its activity.

Acetates↗
PubMed1993

A study of cis-diamminedichloroplatinum(II) suppositories for the treatment of rabbit uterine endometrial carcinoma.

cis-Diamminedichloroplatinum (II) (cisplatin: CDDP) suppositories containing NaCl at different concentrations were prepared as a local chemotherapeutic agent for the treatment of uterine endometrial carcinoma and were administered to rabbits implanted with uterine VX2 tumor. The intrauterine CDDP histological level, as well as the antitumor effects and side effects of the suppositories to the liver and kidney were studied. The results showed high intrauterine tissue CDDP level in all suppository administrations. In particular, the NaCl-added suppositories enhanced the intrauterine CDDP level. As for antitumor effects, while the tumor growth rate of the NaCl-added suppository group was likely to be suppressed, the suppositories could not suppress tumor growth completely. The plasma platinum (Pt) level was 1.5 micrograms/ml or less and that of the liver and kidney was as low as 0.31 to 0.48 micrograms/g. No difference in levels depending on NaCl concentration was observed, nor was any abnormality found in the biochemical analysis including glutamate oxaloacetate transaminase (GOT) and blood urea nitrogen (BUN). Histopathological study revealed the degeneration of tumor cells in the NaCl-added suppository group. Minimal congestion and hemorrhage were observed in the endometria, possibly resulting from CDDP. By adding NaCl to CDDP suppositories, the uterine CDDP level and antitumor effects increased while no serious renal dysfunction was noted. Therefore, we conclude that NaCl-added CDDP suppositories are a useful local chemotherapy for endometrial carcinoma.

Animals↗
PubMed1990

Improvement by adjuvants on the rectal bioavailability of non-absorbable drugs following administration of suppository.

The influence of suppository bases and adjuvants on the release rate of drugs and the absorption of non-absorbable drugs such as sulfanilic acid (SA) and sulfaguanidine (SG), was investigated following the rectal administration of suppositories. The suppository bases used were lipophilic bases such as Witepsol W 35, H 15, S 55, E 75 and hydrophilic base such as macrogol. SA was rapidly released from macrogol, W 35, H 15 and S 55, except E 75. On the other hand, SG was rapidly released from macrogol, whereas the release of SG from lipophilic bases was slow. Rectal absorption of SA and SG following administration of each drug alone in suppository form was slight. On the addition of diclofenac sodium (DF) as absorption promoter the blood levels of SA and SG released from all suppositories increased by about two to four fold compared with those suppositories containing only SA or SG, respectively. However, the absorption of SG still did not attain sufficient levels by the administration of DF only. The rectal absorption of SG was markedly increased by the release rate of the drug from the suppository. These results indicate that after administration of these suppositories the bioavailability of non-absorbable drugs was sufficiently improved by enhancing both the release rate from the suppositories and the rectal membrane permeability.

Adjuvants, Pharmaceutic↗
PubMed1984

Absorption and bioavailability of calcium and magnesium salts of indomethacin from rectal suppositories.

In order to estimate the application to rectum of calcium and magnesium salts of indomethacin (IND), the suppositories of the salts and IND were prepared using macrogol and Witepsol H-15 bases. The rectal administration of these suppositories (Witepsol H-15) was compared with the oral administration of IND and the salts. The hardness, melting point, and liquefaction time of the suppositories were similar between IND and the salts. The in vitro release of IND-Mg from the suppositories was significantly faster than that of IND, while the release of IND-Ca was slower. The area under the plasma drug concentration-time curve (AUC) after IND suppositories was significantly higher than that after oral administration of IND (p less than 0.01). The AUC value after IND-Ca suppositories was slightly higher than those after other suppositories, although the plasma levels in early period after IND-Ca suppositories were lower, indicating the slow absorption of IND-Ca. The multiple treatment with IND-Ca suppositories gave no histological change of the rectal mucosa. Therefore, the present results suggested that IND-Ca was favourable for the rectal administration, in high doses and repeatedly.

Administration, Oral↗
PubMed1992

Prolonged release of morphine alkaloid from a lipophilic suppository base in vitro and in vivo.

The in vitro release characteristics of four suppository formulations of morphine (15 mg) were investigated using the USP rotating basket dissolution apparatus. Morphine hydrochloride in polyethylene glycol (PEG), a hydrophilic suppository base, morphine alkaloid in PEG and morphine hydrochloride in Novata BBC (a lipophilic suppository base) completely released the drug within 25 min whereas, morphine alkaloid in Novata BBC (MAN) released the drug over 10 h. The absorption of the morphine hydrochloride/PEG (MHP) suppository was compared with that of a 15 mg oral solution in eight patients with malignant disease in a crossover design. Time of peak plasma morphine concentration (tmax) was similar for both preparations (1.8 +/- 1.6 h and 1.2 +/- 0.5 h, respectively; p > 0.05), showing that the MHP suppository was rapidly absorbed. The MAN and MHP suppositories were then compared in a further nine patients in a crossover design. Prolonged release of morphine from the MAN suppository was also evident in vivo as tmax (2.5 +/- 1.4 h) was significantly greater than that for the morphine hydrochloride/PEG suppository (0.7 +/- 0.3 h; p < 0.002). There was no significant difference in AUC (0-7 h) (34.5 +/- 19.2 versus 38.9 +/- 16.1 ng.h/ml, respectively; p > 0.05) indicating a similar amount of morphine absorbed. Plasma morphine concentrations were more sustained for 7 h after dosage with the MAN suppository, with lower peak (8.3 +/- 4.9 and 12.3 +/- 6.6 ng/ml, respectively) and higher 6 h plasma morphine concentrations (5.81 +/- 4.85 and 3.30 +/- 1.0 ng/ml, respectively; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Rectal↗
PubMed1989

[Clinical evaluation of buprenorphine suppositories in postoperative patients--plasma concentrations and effects on the respiratory and circulatory system].

The plasma concentrations of buprenorphine were measured and blood gas analysis was done after administration of buprenorphine suppositories (0.2 and 0.4 mg) or its intramuscular injection (0.2mg) in postoperative patients. The C max for 0.4mg suppositories was comparable to that for 0.2mg injection, whereas the T max for suppositories was as large as about 2 hrs in contrast to 1.5 hrs for 0.2mg injection. The size of AUC was in the following order: 0.4mg suppositories greater than 0.2mg injection greater than 0.2mg suppositories. Neither notable increase in PaCO2 nor decrease in respiration rate was observed after administration of the suppositories, indicating that the formulation will not cause clinically significant respiratory depression. No significant changes were observed in blood pressure or pulse rate. Buprenorphine suppositories are considered to be safe for use in postoperative patients. Percent pain relief in the suppository group was smaller than that in the injection group. This appears to be due to a slower rate of increase in the plasma levels of buprenorphine after administration of suppositories than that after intramuscular injection. Therefore, it seems practical to give this drug to postoperative patients before the start of pain.

Administration, Rectal↗