Administration Of Suppositories Research Articles

Sildenafil vaginal suppositories: preparation, characterization, in vitro and in vivo evaluation

Aim: The main objective was to investigate the in vitro release profile/kinetics, and in vivo plasma pharmacokinetics (PK) and organ biodistribution (BD) of the prepared sildenafil vaginal suppositories (SVS).Methods: Suppositories containing 25 mg of sildenafil were prepared by the cream melting technique using Witepsol H-15 as a suppository base. The suppositories were characterized for weight variation, content uniformity, hardness, disintegration time and crystallinity change. The in vitro dissolution in pH 4.5, and in vivo plasma PK and organ BD of sildenafil from SVS in female Sprague Dawley rats, were also investigated.Results: The mean weight variation, content uniformity, hardness and disintegration time of the prepared SVS were 1.127 ± 0.020 g, 98.25 ± 2.50%, 2.5 ± 0.08 kg and 9 ± 1.0 min, respectively. The release of sildenafil from the SVS was more than 90% at 30 min, with a release kinetic of Hixson--Crowell model and non-Fickian diffusion (n = 0.464). The plasma PK study demonstrated a significantly lower Cmax (∼10 times) and AUC0–24 h (∼13 times) of sildenafil in plasma following intravaginal (IVG) administration of suppositories compared to oral (PO) administration of sildenafil solution. Nevertheless, the organ BD study showed a phenomenally higher Cmax (∼40 times) and AUC0–24 h (∼20 times) of sildenafil in uterus following IVG administration of suppositories than PO administration of sildenafil solution.Conclusion: This study demonstrated enhanced sildenafil exposure in the uterus following IVG administration of SVS, which could be used to target the uterus for therapeutic benefits.

Clinical skills series/2: enemas and suppositories

The varied role and function of the healthcare assistant and assistant practitioner (HCA and AP) mean that they may have to care for people who require suppositories or enemas. The administration of enemas and suppositories is seen as an intimate care activity. Suppositories and enemas are used for a variety of reasons and the technique for each is slightly different. This article provides an outline of how to care for a person pre-, peri- and post- procedure; it also outlines how to safely and effectively administer suppositories and enemas. In order to do this correctly, the HCA and AP must have an understanding of the lower gastrointestinal tract. The article provides an overview of the lower gastrointestinal tract in order to promote insight and understanding.

Evaluation of plasma diazepam and nordiazepam concentrations following administration of diazepam intravenously or via suppository per rectum in dogs

To evaluate the pharmacokinetics of diazepam administered per rectum via compounded (ie, not commercially available) suppositories and determine whether a dose of 2 mg/kg in this formulation would result in plasma concentrations shown to be effective for control of status epilepticus or cluster seizures (ie, 150 to 300 ng/mL) in dogs within a clinically useful interval (10 to 15 minutes). 6 healthy mixed-breed dogs. Dogs were randomly assigned to 2 groups of 3 dogs each in a crossover-design study. Diazepam (2 mg/kg) was administered IV or via suppository per rectum, and blood samples were collected at predetermined time points. Following a 6- or 7-day washout period, each group received the alternate treatment. Plasma concentrations of diazepam and nordiazepam were analyzed via reversed phase high-performance liquid chromatography. Plasma concentrations of diazepam and nordiazepam exceeded the targeted range ≤ 3 minutes after IV administration in all dogs. After suppository administration, targeted concentrations of diazepam were not detected in any dogs, and targeted concentrations of nordiazepam were detected after 90 minutes (n = 2 dogs) or 120 minutes (3) or were not achieved (1). On the basis of these results, administration of 2 mg of diazepam/kg via the compounded suppositories used in the present study cannot be recommended for emergency treatment of seizures in dogs.

Use of Intravenous Acetaminophen (Paracetamol) in a Pediatric Patient at the End of Life: Case Report

For the better part of 100 years, acetaminophen (or paracetamol as it is known outside of the United States) has been a common first-line analgesic in pediatrics and is typically well tolerated with minimal side effects. Its use as an anti-pyretic is also well-documented and thus it is used broadly for symptom control in the general pediatric population. In pediatric palliative care, acetaminophen is also used as an adjuvant to opioid therapy for pain as well as an anti-pyretic. For many pediatric patients near end-of-life, however, the ability to tolerate oral intake is diminished and rectal suppository administration can be distressing or contraindicated as in the setting of neutropenia, thus limiting use of acetaminophen by its usual routes. In Europe and Australia, an intravenous formulation of acetaminophen has been used for many years and has only recently become available in the United States. Here, we describe a case using intravenous acetaminophen in a pediatric patient at the end of life.

Usefulness of the Preoperative Administration of Tegafur Suppositories as Alternative Adjuvant Chemotherapy for Patients with Resectable Stage II or III Colorectal Cancer: A KODK4 Multicenter Randomized Control Trial

Objective: The aim of this study was to evaluate the feasibility and conferred protection against recurrence of preoperatively administered tegafur suppositories following the intravenous and oral administration of fluoropyrimidine in a multicenter randomized control trial. Methods: Patients with clinical T3/4 colorectal cancer were randomly assigned to receive the preoperative administration of tegafur suppositories (group A) or no preoperative treatment (group B). The primary end points were disease-free survival (DFS) and overall survival (OS). Results: The mean follow-up periods were 80.9 ± 31.0 months in group A and 64.5 ± 28.8 months in group B. The 5-year DFS rates were 89.3% in group A and 70.3% in group B (p = 0.045), whereas the 5-year OS rates were 91.4% in group A and 73.2% in group B (p = 0.051). Furthermore, a significant difference in the cumulative distant metastatic rate was observed (group A, 7.4% vs. group B, 23.4%; p = 0.03). However, no significant difference in the cumulative local recurrence rate was seen (group A, 4.6% vs. group B, 8.2%; p = 0.68). Conclusion: Despite a relatively small sample size, preoperative tegafur suppositories might protect recurrences and improve survival rates, mainly by preventing distant metastasis. These findings suggest the utility of tegafur suppositories as an alternative neoadjuvant treatment in modern chemotherapy for colorectal cancer.

A randomized comparison of the efficacy, side effects and patient convenience between vaginal and rectal administration of Cyclogest® when used for luteal phase support in ICSI treatment

This study compares the efficacy, side effects and patient convenience of vaginal and rectal routes of administration of progesterone suppositories (Cyclogest) when used for luteal phase support during in vitro fertilization cycles, through the use of antagonist protocols. 147 patients who underwent intra-cytoplasmic sperm injection cycle were randomized on the day of the embryo transfer (ET) by a computer-generated randomization program to receive 400 mg of Cyclogest either vaginally or rectally twice daily for up to 8 weeks. A pregnancy test was conducted 2 weeks after embryo transfer. If the pregnancy test was negative, the application was discontinued. On day 14th after embryo transfer, patient's acceptability and side effects were assessed using a questionnaire which was given to the patients on the day of ET prior to performing the pregnancy test. The clinical pregnancy rate at the 8th week of gestation and the level of luteal progesterone were evaluated. There were no substantial differences in the demographics or other characteristics between the two groups. There were no significant differences in serum P concentration 6 days after ET, the clinical pregnancy and abortion rates. The difficulty of administration route, the discomforts experienced following administration, and the proportion leaking out on the 14th day were similar between the two groups. Significantly more patients administering the medication per vagina had perineal irritation (21.3 vs. 2.2 %). The prevalence of tenesmus (35.1 vs. 21.1 %) and rectal itching (26.7 vs. 2.8 %) were significantly more in rectal route. This study demonstrates that the efficacy of Cyclogest is similar when administered via both the vaginal and rectal routes. Although their side effects differ, the ease of administration for patients and their preference are similar.

Premarketing Surveillance of Ibuprofen Suppositories in Febrile Children

In many countries, ibuprofen is available only in oral formulations. The authors aimed to investigate parental satisfaction and possible adverse reactions among children receiving newly marketed ibuprofen suppositories, prior to their arrival at the pharmaceutical points of distribution. Children needing antipyretic medication were recruited from 11 pediatric wards and clinics in Israel. Each patient received ibuprofen suppositories (5-10 mg/kg/dose) after completing a data collection form. After 3 to 7 days of treatment, information regarding parent satisfaction, possible adverse reactions, and concomitant use of drugs was obtained. Overall, 490 children completed the study. Parents' satisfaction was high (4.5 ± 0.47 on a scale of 1-5), and 92.2% reported that they would use the medication in the future. Adverse reactions were reported in 8 patients (1.63%, 95% confidence interval = 1.77-3.25), the most common being diarrhea. Rectal administration of ibuprofen suppositories is well tolerated and overall satisfaction and the repeated expected use were high.

Clinical Studies on the Termination of Pregnancy by the Vaginal Administration of 16, 16-Dimethyl-Trans-Δ2-PGE1 methyl Ester (ONO 802)

A prostagladin analogue, 16-16-Dimethyl-trans-Δ2-PGE1 methyl ester from ONO Pharmaceutical Co., Ltd. was studied by the vaginal administration of suppositories for termination of early and 2nd trimesters of pregnancy. Clinical efficacy and side effects were observed and evaluated.

Parental Substance Abuse and Accidental Death in Children

In this report, the authors present two cases of accidental death in children of addicted parents. In the first case, the child was left unattended at home while the mother went out to buy cocaine. She was arrested and detained with no mention of the unsupervised child. The cause of death in this case was determined to be starvation and dehydration. In the second case, a child mistakenly received a methadone suppository by her father instead of an antipyretic suppository. Toxicological analysis of the femoral blood revealed methadone at a concentration of 1.2 mg/L. The cause of death was determined to be methadone intoxication. The literature is reviewed and discussed. We report these cases to illustrate the risk of harm to children from illicit drugs and prescription medications at home and because there is no mention of accidental death in children following a methadone suppository administration in the current literature.

Effect of Rectal Diclofenac in Reducing Postoperative Pain and Rescue Analgesia Requirement after Cardiac Surgery

Adequate analgesic medication is mandatory after coronary artery bypass grafting (CABG) surgery. The aim of this study was to assess the analgesic efficacy, side effects, and need for rescue analgesia after CABG surgery comparing diclofenac and placebo rectal suppository. Thirty-seven consenting adults undergoing elective CABG surgery were randomly assigned in a double-blind fashion to receive either rectal diclofenac 100 mg (Group 1, n = 19) or placebo suppository (Group 2, n = 18) postoperatively, just after extubation. Both groups were given intravenous tramadol as a rescue analgesic. Pain scores in the two groups were assessed on a 10-cm visual analog scale at 0, 0.5, 1, 1.5, 2, 6, 12, 18, and 24 hours after suppository administration. Rescue analgesic consumption, sedation, nausea, and vomiting in both the groups were also recorded. Twenty-four-hour tramadol consumption in Group 1 was 92.5 +/- 33.5 mg compared to 157.5 +/- 63.4 mg in Group 2 (P = 0.002). Patients in the placebo group had significantly greater pain scores 1.5 to 12 hours after extubation. Group 1 patients were significantly more awake compared to Group 2 (P < 0.05). The incidence of postoperative nausea was less in Group 1 than in Group 2 (P = 0.001). Though not statistically significant, three patients in Group 2 each had a single episode of vomiting, whereas no patient had vomiting in Group 1. Rectal diclofenac suppository with tramadol provides adequate pain relief after cardiac surgery, and also reduces tramadol consumption and side effects commonly associated with tramadol.

Pharmacokinetics of tramadol and its major metabolites following rectal and intravenous administration in dogs

AIM: To compare the rectal and I/V administration of tramadol in dogs, to assess both its pharmacokinetic properties and absolute bioavailability. METHODS: After rectal administration via suppositories and I/V injection of tramadol (4 mg/kg), the concentration of tramadol and its main metabolites, O-desmethyl-tramadol (M1), N-desmethyl-tramadol (M2) and N,O-didesmethyl-tramadol (M5), were determined in plasma, using high-performance liquid chromatography (HPLC). A balanced cross-over study was used, involving six male Beagle dogs. RESULTS: Plasma concentrations after rectal and I/V administration were fitted on the basis of mono- and bi-compartmental models, respectively. Following rectal administration tramadol was detected from 5 minutes up to 10 hours, in lesser amounts than M5 and M2, while M1 was detected in negligible amounts. Following I/V administration tramadol was detected up to 10 hours, M2 and M5 were detected at similar concentrations, and M1 was present at low concentrations. The area under the curve (AUC) of the three metabolites did not differ significantly after either route of administration of tramadol. The absolute bioavailability of tramadol via rectal administration was 10 (SD 4)%. CONCLUSIONS: After rectal administration of tramadol suppositories, absorption of the active ingredient was rapid, but its metabolism quickly transformed the parent drug to high levels of M2 and M5. CLINICAL RELEVANCE: In the dog, rectal pharmaceutical formulation of tramadol would have a different pharmacokinetic behaviour than in humans.

In vivo and in vitro characterization of rifampicine suppositories

In this research, rifampicin suppositories were prepared due to the easy use of suppository administration in the elderly and the fact that plasma concentrations are higher than tablets. The suppositories were formulated with 100 mg of rifampicin using different bases, namely Witepsol H15, Witepsol S58, Witepsol E76, Polyethylene glycol PEG (two different formulations) and modified glycerogelatin (MGG) using the melting method. To optimize the drug release rate, different enhancers such as sodium lauryl sulfate (SLS) as an ionic surfactant, as well as Brij 92 as non-ionic surfactants, and Cetrimide as a cationic surfactant in different concentrations were chosen. The highest release of rifampicin was observed with formulations containing 0.4% SLS in Witepsol S58, 1.2% Cetrimide in Witepsol S58 and 0.4% Brij 92 in PEG2. The drug plasma levels after rectal administration were compared to those obtained after oral administration of the same dose. After 4 h, C max of rifampicin was 23.91 ± 2.74 μg/mL for the oral suspension vs. 43.03 ± 1.76 and 28.90 ± 1.37 μg/mL for PEG2 with 0.4% Brij 92 and Witepsol H15 with 1.2% Brij 92 suppositories. The comparative bioavailability of rifampicin from PEG2 with 0.4% Brij 92 and Witepsol H15 with 1.2% Brij 92 suppositories were 207.42 and 148.31% respectively, in relation to that after oral administration.

Safe use of rectal suppositories and enemas with adult patients

Medications that are given via the rectal route are prescribed for a variety of reasons and have either a local or systemic effect. The administration of suppositories and enemas is an intimate procedure which has the potential to cause embarrassment and discomfort for the patient. This article outlines the reasons for the use of rectal medications and recommends a procedure to be followed when giving them.

Rectal suppository insertion: the reliability of the evidence as a basis for nursing practice

This paper considers the correct method for inserting a rectal suppository, both as a medication and also to achieve bowel evacuation. The aim is to find out whether the correct method is blunt end or pointed end foremost. It follows from a question raised by a third year student nurse. In the classroom, she had been taught that the correct method for the administration of a suppository for systemic absorption was to insert it blunt end foremost into the rectum. However, if the suppository was to be used for evacuant purposes, it should be given pointed end foremost. In clinical practice, however, she was told the suppository should always be inserted pointed end foremost in all cases, whatever the purpose. This article seeks to clarify the dilemma by examining the sources of evidence underpinning different methods for inserting a rectal suppository. Hence, the literature on the insertion of rectal suppositories was gathered as systematically as possible from medical journals and textbooks, nursing journals and textbooks and manufacturers' information to patients. Having gathered the literature, this was examined, appraised and critically analysed for rigour, coherence and reliability. The review of the literature appears to show that evidence adduced for inserting the suppository blunt end foremost derives from one study published in the Lancet in 1991, which challenged 'commonsense'. There did not appear to be other, more recent research. On the other hand, manufacturers' information to patients states generally that the suppository should be inserted pointed end foremost. This has direct relevance for the administration of suppositories and also raises questions as to how research may become integrated into healthcare practice without adequate justification. An article published in the Lancet in 1991 has had a fundamental effect on nursing practice, but has not been subject to scrutiny. The advice given in this Lancet article differs from that currently given by most manufacturers of suppositories, which involves the terms of their product licence. Hence, there is a potential for problems with legal liability should an untoward event arise. Inserting rectal suppositories, whether as a medication or to achieve bowel evacuation, is a very common healthcare practice. Currently, there is inconsistency and discrepancy in the correct method for this procedure in both nursing education and practice. This paper examines the reliability of existing evidence and shows the need for further work in order to provide a reliable evidence base for this commonplace clinical procedure.

A pilot study evaluating the safety and effectiveness of Lactobacillus vaginal suppositories in patients with recurrent urinary tract infection

Changes in the indigenous vaginal microflora with uropathogenic bacteria can predispose women to frequently recurring bacterial cystitis. Lactobacilli used as probiotics have played an important role in preventing the colonization of pathogenic bacteria in the vagina. A prospective clinical pilot study was performed to confirm the safety and effectiveness of Lactobacillus vaginal suppositories against the recurrence of bacterial urinary tract infection (UTI). The patients enrolled in the study were instructed to administer vaginal suppositories containing the strain Lactobacillus crispatus GAI 98322. A significant reduction in the number of recurrences was noted, without any adverse complication ( P = 0.0007). The administration of vaginal suppositories containing L. crispatus GAI 98332 seemed to be a safe and promising treatment for the prevention of recurrent UTI.

Die vaginale Anwendung von natürlichem Progesteron als Lutealphasenunterstützung nach IVF und Embryotransfer

The beneficial effect of luteal phase support after embryo transfer in IVF treatment (IVF-ET) has unequivocally been accepted. Various substances (human chorionic gonadotropin (hCG), progesterone (P), estradiol [E2]) and regimens of administration are employed. The present systematic review aims at determining the efficacy of administration of vaginal Pas capsules, suppositories or vaginal cream versus other forms of luteal phase support (including Crinone® 8% vaginal gel) after ovarian hyperstimulation and IVF-ET. The available literature was reviewed and data on clinical pregnancy rates per embryo transfer was retrieved from randomised controlled trials. 24 studies with a total of 5334 randomized patients in 33 group comparisons were included in this review. In these studies, various doses of vaginal P as capsules/suppositories/vaginal cream in various administration regimens were evaluated. The following subgroups were identified: vaginal P vs. 1) intra-muscular P (odds ratio [OR] 0.99 [95% confidence interval {CI} 0.58-1.72]); 2) hCG (1.13 [0.84-1.52]); 3) vaginal P + hCG (1.02 [0.76-1.36]); 4) Crinone® 8% (0.96 [0.76-1.22]); 5) vaginal P + oral E2 (1.03 [0.68-1.56]); and 6) orally administered P or gestagen (1.11 [0.69-1.76]). Results of individual studies were homogenous in subgroup comparisons except for vaginal P vs. intra-muscular P. Current data from the literature indicate no significant difference between vaginal Pas capsules/suppositories/cream as compared to a wide range of other forms of luteal phase support after IVF.

Enhanced Anticancer Effect but Low Hepatotoxicity of Clotrimazole Solid Suppository with Poloxamer188 and Propylene Glycol in Mouse Tumor Model

Clotrimazole, an antifungal imidazole derivative, has been shown to inhibit the proliferation of normal and cancer cells in vitro and tumor growth in vivo. Also, it is known as a potent inhibitor of angiogenesis. However, clinical application of clotrimazole has shown hepatotoxicity possibly associated with the imidazole moiety. The present study assessed the anticancer efficacy and side effects of clotrimazole rectal suppository administration by comparing with oral route. The rectal suppository was made with 70% poloxamer 188 (P188) and 30% propylene glycol (PG), which was a solid phase at room temperature and instantly melted at physiological temperature. The two types of syngenic mouse tumor model (rectal and skin tumor) were generated. Clotrimazole treatment, which started after the tumor has developed, decreased the tumor size in the route of both oral and rectal suppository administration. However, the decrease in the tumor size and the survival rate of the mice were significantly higher in the group treated with rectal suppository than in the group treated with oral administration. In addition, the hepatotoxicity assessed as the activity of glutamate oxaloacetate transaminase and hepatic lipid peroxidation was significantly higher in the mice treated with clotrimazole through oral route than rectal suppository.

In-vitro and in-vivo availability of mebeverine hydrochloride suppositories

Mebeverine hydrochloride suppositories were prepared using Witepsol H15 suppository base. The effect of different concentrations of various enhancers (surfactants, amino acids and osmotic modifiers) on the drug release form the prepared suppositories was studied. The results showed that mebeverine hydrochloride suppositories containing Brij 35 (2%) and urea (10%) were superior to the other formulations containing the tested enhancers. These formulae showed the highest release rates (K = 0.083 ± 0.004 min-1 and 0.111 ± 0.005 min-1 , respectively) that followed first-order kinetics with t50% of 8.35 ± 0.45 min and 6.24 ± 0.33 min, respectively. Therefore, these two formulae with the control suppositories were subjected to in vivo study in albino rabbits compared to the commercial Duspatalin® tablets and intravenous injection. Higher Cmax (1770.26 ± 165.46 ng.ml-1) within shorter Tmax (0.75 ± 0.20 h) was observed after rectal administration of the control suppositories compared to that of commercially available film-coated tablets (Duspatalin® – 135 mg). A significant difference (p≤0.05) between the absolute bioavailability of Duspatalin® tablets (27.09 ± 3.80%) and control suppositories (46.66 ± 1.72%) was detected. Statistically (p≤0.05), the mean residence time (MRT) after oral administration of Duspatalin® tablets (3.16 ± 0.30 h) was significantly longer than that after the rectal administration of control suppositories (2.73 ± 0.30 h). suppositories containing 2% Brij 35 showed higher plasma levels of the drug (2766.11± 339.50 ng.ml-1) with an absolute bioavailability of 70.50 ± 10.51% compared to 27.09 ± 3.80% for Duspatalin® tablets.

直腸がん術後骨転移のがん性疼痛に対しフェンタニル持続注入とジクロフェナク坐剤人工肛門内長期投与が有効であった１例

直腸がん術後骨転移のがん性疼痛に対しフェンタニル持続注入とジクロフェナク坐剤人工肛門内長期投与が有効であった１例

Effect of Simultaneous Insertion of Oleaginous Base on the Absorption and on the Anticonvulsant Effect of Diazepam Suppository

To clarify the drug-base interaction between diazepam (DZP) suppository and oleaginous base, we investigated the effect of simultaneous combination of oleaginous base on the absorption and on the anticonvulsant effect of DZP Suppository in rats. Simultaneous insertion of DZP suppository and oleaginous base significantly decreased maximum concentration (C(max)) and area under the blood concentration-time curve (AUC) of plasma DZP concentrations. Administration of DZP suppositories (2.5, 5 mg/kg) dose-dependently suppressed the pentylenetetrazol (PTZ)-induced seizures, and the anticonvulsant effect of DZP suppository (5 mg/kg) was reduced by simultaneous insertion of oleaginous base. In an in vitro study using a suppository release apparatus, simultaneous combination of DZP suppository and oleaginous base (1.5-98 mg) significantly decreased the accumulative release of DZP in a dose-dependent manner. These results suggested that when DZP suppository and oleaginous base are inserted simultaneously, the released DZP distributes partially to the oleaginous base, and this phenomenon is related to the decreases in the plasma concentration and the anticonvulsant effect of DZP.