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Treatment of non-albicans Candida vaginitis with amphotericin B vaginal suppositories.

OBJECTIVE: This study was undertaken to investigate whether amphotericin B vaginal suppositories would be effective in the treatment of non- albicans Candida vaginitis in women who failed conventional therapy. STUDY DESIGN: Thirty-two patients were identified with non- albicans Candida vaginitis. These patients were treated with conventional antifungal agents. Ten patients had persistence of the non- albicans Candida infection after treatment. Amphotericin B 50-mg vaginal suppositories were given nightly for 14 days to this subgroup of treatment failures. RESULTS: Of 10 women, 8 (80%) who were treated with amphotericin B vaginally initially showed no further infection. One of the treatment successes had 2 recurrences and responded to a second course of amphotericin B but failed a third course. If this patient is considered a treatment failure, then amphotericin B vaginal suppositories were successful in 70% of patients. The medication was well tolerated and local side effects were minimal. CONCLUSION: Amphotericin B vaginal suppositories are a viable treatment option for refractory vaginitis caused by non- albicans Candida .

Administration, Intravaginal↗

[Premature termination of pregnancy in the 2nd and 3rd trimester. Serial administration of 1 mg gemeprost vaginal suppositories versus intravenous sulproston].

Comparison of 1 mg Gemeprost-Vaginal Suppositories Serial Application versus Sulproston i.v.: Three different regimens for the termination of second and third trimester pregnancies by the use of prostaglandins (PG) were compared in a retrospective analysis. In group A (n = 16) terminations were attempted by continuous i.v. Infusion of Sulproston 9 hours after administration of a 3 mg-PGE2-vaginal tablet overnight. In group B (n = 22), i.v. Sulproston was started 2 hours after priming with 1 mg Gemeprost-vaginal suppositories. The outcome of these two regimens was compared with that of repeated administration of 1 mg Gemeprost-vaginal suppositories at 6-hourly intervals (group C, n = 25). In each group. If uterine contractions failed to appear after one day, the treatment was discontinued for a sleep rest over night and then resumed. Genetic disorders or fetal malformations were the most frequent reasons for termination. Patients with intrauterine fetal demise, rupture of the membranes, preterm labour or a ripe cervix (Bishop Score > 3) were excluded. Median time intervals from induction to abortion were 33 hours in group A and 23 hours in each Group B and C. The rate of fetal expulsions within 12, 24 and 36 hours in groups B and C were similar. Women of parity > or = 1 showed significantly shorter intervals than nulliparae in groups A and C. Only one woman (in group A) failed to expel after induction, in four other cases (in groups A and B) complications (local thrombophlebitis, bronchospasm) were noted. The serial administration of 1 mg Gemeprost-vaginal suppositories at 5-hourly intervals showed fewer side effects and seems to be as efficient as sulproston i.v. after cervical ripening.

Abortifacient Agents, Nonsteroidal↗

A comparison of intermittent vaginal administration of two different doses of misoprostol suppositories with continuous dinoprostone for cervical ripening and labor induction.

PURPOSE: To compare the efficacy of a vaginal insert administering continuous dinoprostone with vaginal suppositories containing two different doses of misoprostol for cervical ripening and induction of labor. STUDY DESIGN: In this prospective, randomized, double-blinded study, 118 patients with indications for induction of labor and an unfavorable Bishop score were randomly assigned to receive either continuous dinoprostone, misoprostol 35-microg suppositories, or misoprostol 50-microg suppositories. RESULTS: No significant differences were noted among the three groups in the change of Bishop score, induction of active labor or the time from initial treatment to delivery. Active labor occurred in roughly two-thirds of the patients in an average of about 5.7-6.7 h regardless of treatment assignment. When the two misoprostol groups were combined, a shorter interval from insertion to vaginal delivery was observed in the nulliparous women receiving misoprostol than those receiving continuous dinoprostone (21.3 vs. 27.2 h, p = 0.019). Except for the significantly lower incidence of tachysystole observed in the combined misoprostol group (3.8% vs. 15.4%, p = 0.036), there were no other significant differences between the groups in mode of delivery or in adverse maternal, fetal, or neonatal effects. CONCLUSION: Misoprostol suppositories appeared to be as effective and safe as continuous dinoprostone in inducing cervical ripening in this sample.

Administration, Intravaginal↗

The release of isoconazole nitrate from different suppository bases: in-vitro dissolution, physicochemical and microbiological studies.

The influence of the suppository base on the in-vitro release of isoconazole nitrate was studied by dissolution, physicochemical diffusion and microbiological disk-diffusion methods. Vaginal suppository formulations containing 25 mg isoconazole nitrate for local treatment of vaginitis were prepared by a fusion method, using different hydrophilic and lypophilic suppository bases (PEG 6000, PEG 4000, PEG 1500, Witepsol H15, Novata BD and Cremao). In-vitro release rates were examined by dissolution, physicochemical diffusion and microbiological disk-diffusion methods. In the physicochemical investigations the pH indicators (pH 1-14) erythrosin B, thymol blue, bromocresol green, chlorophenol red, phenol red, and alkali blue were added to agar gels. The discs were placed onto the agar gels and 21 h later, the coloured zone diameters were measured. In the microbiological investigations, the discs were put on the inoculated plates with the suspension of Candida albicans (Institute Pasteur 628). The inoculated plates were incubated at 37 degrees C for 3 days, then the diameters of inhibition zones were measured. In the dissolution investigations release rates were in the order PEG 6000 > PEG 4000 > PEG 1500 > > Witepsol H15 > Cremao > Novata BD. The diffusion distance of isoconazole nitrate in the physicochemical investigation was in the order polyethylene glycols > Witepsol H15 > Novata BD. In the microbiological studies release rates were found with polyethylene glycols > Witepsol H15 > Novata BD > Cremao. The findings in the in-vitro studies suggested that polyethylene glycols are suitable bases for vaginal suppositories.

Antifungal Agents↗

The release of isoconazole nitrate from different suppository bases: in-vivo release of drug labelled with 99mTc in rabbits.

The influence of the suppository bases on the in-vivo release of 99mTc-labelled isoconazole nitrate was investigated. The single-dose vaginal suppository formulations for local treatment of vaginitis were prepared by a fusion method using polyethylene glycols, Witepsol H15, Novata BD and Cremao. Prepared vaginal suppositories containing solid-labelled substance were applied to the vagina of rabbits and at 0, 2 and 24 h after administration, the amounts of radioactivity in the vagina were detected by the SPECT Gamma Camera and the release rates of the drug were calculated. The percent released was found to be in the following order; polyethylene glycol (PEG) 6000 > PEG 4000 > Witepsol > PEG 1500 > Novata BD > Cremao. The results obtained in both in-vitro and in-vivo studies indicated that the vaginal suppository of isoconazole nitrate prepared with polyethylene glycols could confidently be used in therapy.

Animals↗

Efficacy of povidone-iodine vaginal suppositories in the treatment of bacterial vaginosis.

A prospective, randomized clinical trial was performed to study the efficacy of povidone iodine (Betadine) suppositories for the treatment of bacterial vaginosis (BV) in comparison to capsules containing lactobacilli (Döderlein Med). Seventy patients with BV included in the study were randomly assigned to be either treated with povidone iodine suppositories or lactobacilli. Patients were treated once a day for 5 days. Initial examinations took place on the first day of the study with follow-up examinations on days 8 and 15. The examinations included clinical parameters, patient evaluation, secretion screens, and quantitative and qualitative microbiological tests of vaginal flora. Both treatment groups showed improvement of clinical parameters, condition of secretions and subjective state of health. At day 15 there was a trend towards a better efficacy of the treatment with povidone iodine but this was not significant. However, patients with acute BV treated with povidone iodine had significantly better scores after 15 days. Both treatments were well tolerated. The microbiological examinations showed an increase of the mean number of lactobacilli in the vagina on day 8 after initiation of treatment with lactobacilli, but a decrease on day 15. Contrary to that the lactobacilli counts from patients treated with povidone iodine suppositories decreased after the first week but increased in the second one. Potentially pathogenic germs, e.g. Gardnerella, Bacteroides and Enterobacteria were reduced in a higher extent and with a longer lasting effect after treatment with povidone iodine suppositories than with capsules containing lactobacilli. The results of this study show that native lactobacilli rapidly re-colonize after the antiseptic treatment with povidone iodine. Therefore, there is no need to use lactobacilli in addition.

Adolescent↗

A comparison of the local tolerability, safety and efficacy of meloxicam and piroxicam suppositories in patients with osteoarthritis: a single-blind, randomized, multicentre study.

The local tolerability, safety and efficacy of meloxicam 15 mg suppositories were compared with piroxicam 20 mg suppositories over a 3-week period in a single-blind, randomized study in patients with osteoarthritis. Patients were randomized 2:1 to receive meloxicam (n = 216) or piroxicam (n = 109). More than 90% of patients and investigators assessed local tolerability of both treatments as good or very good (primary endpoint). There was no significant difference between the groups. Global efficacy was reported by approximately 80% of patients in both groups to be good or very good. Pain on movement and at rest and joint mobility showed statistically significant improvements compared with baseline with both meloxicam and piroxicam; there were no statistically significant differences between treatment groups. Piroxicam and meloxicam suppositories were equally well tolerated, with no serious adverse events recorded in either treatment group. Local adverse events occurred in 11.9% of patients receiving piroxicam and 6.9% of those receiving meloxicam. Overall, gastrointestinal adverse events were the most frequent of all 11.9% of piroxicam-treated patients). In both groups, about 90% of global tolerability assessments were classified, by the investigator and the patient, as either very good or good. In conclusion, meloxicam 15 mg suppositories showed excellent local tolerability accompanied by good safety and efficacy in osteoarthritis, which was comparable to that of an established non-steroidal anti-inflammatory drug (NSAID) administered by the rectal route, and to that previously observed with oral formulations of meloxicam 15 mg.

Adult↗

[Formulation and in vitro investigation of antibacterial vaginal suppositories. Part 1. Considerations in selecting the vehicle. Methods and results of the physical examination].

Vaginal suppositories frequently used in gynaecological therapy were studied. Several antibacterial pharmacons are used for the topical treatment of vaginitis of various origins. However, the choice of the vaginal suppository base was often considered to be of minor importance for a long time. In view of the fact that the liberation of the given active substance and the subsequent therapeutic effect may be improved or inhibited by the vehicle, their aim was to find the optimal suppository base for vaginal suppositories containing sulphadimidine, chloramphenicol and gentamicin-sulphate by means of in vitro experiments. On the basis of breaking hardness, disintegration time and spreading properties the French Suppocire NA product, and compositions of macrogols with lower molecular weight proved to be the best lipophilic and hydrophilic bases respectively.

Anti-Infective Agents, Local↗

Local treatment of colpitis with Betadine vaginal suppository.

Observations made with Betadine vaginal suppository in the treatment of 60 women suffering from colpitis have been discussed. The results of microbiological examinations of vaginal discharge sampled before 1 week and 4 weeks after the onset of therapy were compared. The effectiveness, tolerance of therapy, and the subjective opinion of the treated women were analysed. According to the results of the examinations in response to Betadine vaginal suppository the positivity of vaginal discharge for Candida decreased from 16 to 3 cases, for Trichomonas from 8 to 1 case, for aerobic bacteria from 16 to 7 cases, and the occurrence of mixed infections from 20 to 2 cases. Subjective complaints, burning, stinging sensation were rapidly moderated. In 52 of the 60 women discharge ceased, in another 4 cases it significantly decreased. In 51 cases burning sensation in the vagina ceased, and in 5 women it significantly decreased. Recurrence was not observed when a control examination was done after 1 month. The women tolerated Betadine vaginal suppository well and found it effective and easily applicable. At the beginning of treatment burning sensation was aggravated in 3 cases. These patients refused to further participate in the examination and received systemic treatment. Due to its broad bactericidal, fungicidal, protozoicide action and its good tolerability Betadine suppository was found to be useful for the local treatment of colpitis.

Administration, Intravaginal↗

Effect of 15(s)15-methyl-PGF2alpha-methyl ester vaginal suppositories on circulating hormone levels in early pregnancy.

Intravaginal administration of 15-methyl-PGF2alpha-methyl ester in the form of suppositories terminated pregnancy in 70 percent of the cases whose last menstrual periods ranged from 35 to 56 days. The use of these suppositories in 49 patients, between 57 to 80 days of gestation, dilated the cervix by 10 mm or more, in one hundred percent of the cases. A decrease in circulating levels of estradiol-17beta and progesterone was observed following 15-methyl-PGF2alpha administration. The mean estradiol-17beta levels declined by about 55.9 percent at 9 hours whereas, the corresponding fall in progesterone was 32.7 percent. This was indicative of a direct action of 15-methyl-PGF2alpha on the corpus luteum. The vaginal use of 15-methyl-PGF2-alpha-methyl ester suppositories thus appears to be a promising method for the termination of early pregnancy and for pre-operative cervical dilatation. The termination of early pregnancy appears to be partly due to the luteolytic effect of 15-methyl-PGF2alpha besides stimulating uterine contractions.

Abortion, Induced↗

Preabortion cervical dilatation with a low-dose prostaglandin suppository. A comparison of two analogs.

Vaginal administration of PGE2 and PGF2 alpha suppositories resulted in cervical changes that facilitated suction curettage termination of 46 first-trimester pregnancies. When 30 mg of 9-deoxo-16,16-dimethyl-9 methylene PGE2 was compared with 0.5 mg of 15(S)-methyl PGF2 alpha suppositories, the cervix-ripening properties of these two agents appeared to be equivalent. Within one to two hours of insertion, a mean dilatation increase of 3.3 and 3.1 mm was achieved for the PGE2 and PGF2 alpha groups, respectively, increasing the ease of suction abortion. Blood loss and gastrointestinal side effects were minimal for both groups. The rapid effectiveness of these suppositories for cervical priming permits a one-day hospital stay for abortion and may minimize long-term sequelae associated with forceful mechanical dilatation of the cervix.

16,16-Dimethylprostaglandin E2↗

Determination of the population pharmacokinetic parameters of sustained-release and enteric-coated oral formulations, and the suppository formulation of diclofenac sodium by simultaneous data fitting using NONMEM.

Data from sustained-release and enteric-coated oral formulations, and the suppository formulation of diclofenac sodium are fitted simultaneously using NONMEM and the general linear model, ADVAN 5. Absorption and disposition parameters, serum levels, and absorption profiles were determined. The in vivo absorption profiles were determined using the program TOPFIT. The in vivo absorption for the sustained-release formulation is slow first order and follows a flip-flop model since disposition rate constants are greater than absorption rate constants. Absorption from the enteric-coated form is essentially complete (> or = 95%) at about 7.5 h, while it is 95% complete at 24 h from the sustained-release formulation. This suggests likely absorption from the colon in the case of the sustained-release formulation since absorption is only 75% complete during the first 10 h. The sustained-release relative bioavailability is 90-99%. Absorption from the suppository is essentially complete at about 4.5 h. However, the relative bioavailability of the suppository formulation is low (55%), since defecation may remove the drug from the absorption site before complete absorption.

Administration, Oral↗

Physical stability of semisynthetic suppository bases.

Changes in the melting range of several semisynthetic suppository bases were studied over time. X-ray diffraction studies characterized the changes as amorphous to crystalline transitions, with likely polymorphic effects occurring concurrently. Use of a modified Krowczynski apparatus to test pure base and single-ingredient suppositories showed dramatic hardening of the materials over periods as short as 6 weeks. Data were obtained by differential scanning calorimetry on freshly solidified, incrementally aged, and equilibrated samples. These methods may be used as both predictive and ongoing physical stability tests in the evaluation of suppository bases and formulas.

Calorimetry↗

HPLC analysis of indomethacin and its impurities in capsule and suppository formulations.

Indomethacin and its impurities in suppository and capsule formulations were quantitatively determined by HPLC using a reversed-phase, octadecyl column and a mobile phase of methanol-water-acetonitrile-acetic acid (55:35:10:1). Analysis of the suppository formulations provided a mean potency for indomethacin of 103.8%. The same formulation was found to contain 4-chlorobenzoic acid (0.02%), 5-methoxy-2-methyl-3-indoleacetic acid (0.07%), 4-chlorobenzoic acid-alpha-monoglyceride (0.39%), and indomethacin-alpha-monoglyceride (0.9%) as impurities. The latter two impurities were a result of the interaction of indomethacin and 4-chlorobenzoic acid with glycerin used in the suppository base. Capsule formulations were likewise assayed with an average potency of 99.9 and 101.5% for 25- and 50-mg dosage forms, respectively. Only one of the two capsule formulations examined contained detectable quantities of 4-chlorobenzoic acid (0.05%).

Capsules↗

Topical treatment with 5-aminosalicylic in distal ulcerative colitis by using a new suppository preparation. A double-blind placebo controlled trial.

Sixty-two patients with ulcerative colitis localised to the distal sigmoid colon and rectum (less than 20 cm) entered the trial. Thirty-two were treated with 5-ASA 500 mg suppositories (Asacol) 3 times a day for 1 month while 30 received a placebo given in the same regime. Clinical, sigmoidoscopic and histological assessment was carried out before, after 15 days and after 1 month of treatment. At the end of the study 5-ASA suppositories showed significantly better results in all the parameters recorded than placebo (p less than 0.01). There were no unwanted effects related to the use of suppositories. This treatment should therefore be offered as a first choice for patients with distal rectosigmoiditis.

Adult↗

Preoperative combined treatment with radiation, intraluminal hyperthermia, and 5-fluorouracil suppositories for patients with rectal cancer.

A clinical trial of a novel modality consisting of preoperative irradiation and intraluminal hyperthermia therapy, with or without 5-fluorouracil (5-FU) suppositories, was conducted on 30 patients with rectal cancer. To create hyperthermia in rectal cancer, an intraluminal electrode connected to a radiofrequency system was devised. Patients were treated preoperatively with a total irradiation dose of 30 Gy, being 3 Gy every 2 days, and 5 applications of hyperthermia given twice a week, with or without 5-FU suppositories, given as 100 mg a day to a total of 2,000 mg. Twenty patients received irradiation, intraluminal hyperthermia, and 5-FU suppositories, being the three-combination treatment, and the remaining 10 received irradiation and intraluminal hyperthermia, being the two-combination treatment. Shrinkage of the rectal cancer was observed macroscopically in 26 patients, resulting in a flattened cancerous crater or shallow ulcer. Microscopic examination revealed a marked decrease in the number of cancer cells. In fact, three resected specimens showed no evidence of cancer cells microscopically. These striking reductions in cancer size enabled us to successfully perform super-low anterior resections in four patients, with anastomoses being made just above the dentate line with a sufficiently safe margin. No serious complications were encountered in this series.

Aged↗

Rectal administration of paracetamol: a comparison of a solution and suppositories in adult volunteers.

The pharmacokinetics and tolerability of two dosage forms for rectal administration of paracetamol were compared. A fatty suppository was compared with a solution of 60 mg/ml paracetamol. Both dosage forms were given as 1000 mg doses to 10 healthy adult volunteers. The solution produced peak plasma concentrations significantly faster (t (max)) than did the suppository. The peak concentration (C(max)) and the area under the curve (AUC(6)) were also significantly greater. The pharmacokinetic characteristics of the solution were superior to those of the suppository. No difference in irritation score was identified and no discomfort was reported.

Acetaminophen↗

Relative bioavailability of a paracetamol suppository.

The relative bioavailability of a new paracetamol suppository (Panodil) and tablets in doses of 0.5 and 1 g was investigated in eight healthy subjects. The tablets were absorbed faster and higher peak plasma concentrations were obtained than after the suppositories. The bioavailability of the suppositories was approximately 80% of that of the tablets at both dose levels. There was no indication of capacity-limited elimination at either the two doses investigated.

Acetaminophen↗