Sertaconazole 300 mg versus clotrimazole 500 mg vaginal suppository for treating pregnant women with acute vaginal candidiasis: a double-blinded, randomized trial.

BACKGROUND: Vaginal candidiasis (VC) commonly affects pregnant women. Traditionally, clotrimazole vaginal tablets (CLO) have been the cornerstone of management. However, sertaconazole ovules (SER) offer a novel topical antimycotic option. This double-blinded, randomized trial evaluated the efficacy of single-dose SER and CLO in treating acute VC during pregnancy. METHODS: From June 2020 to May 2021, this trial recruited pregnant women aged ≥ 18 years with VC symptoms (abnormal vaginal discharge and/or vulvar/vaginal itching) confirmed by microscopy. Participants with ≥ 4 VC episodes in the prior year, immunocompromised status, or imidazole contraindications and those who were absent at the 2-week follow-up were excluded. Participants were randomized to receive either 300 mg SER or 500 mg CLO. Evaluations 2 weeks after the initial medication administration included clinical cure (self-reported resolution of all symptoms), microscopic cure (pseudohyphal absence), patient satisfaction, side effects, and time to clinical cure. Participants with persistent VC received weekly SER doses until delivery. Assessments of recurrence and pregnancy outcomes were done. RESULTS: The analysis included 96 participants (48 per group, mean age 27.4 ± 7.4 years, gestational age at diagnosis 22.9 ± 6.4 weeks). Without statistical significance, SER achieved a higher clinical cure rate (62.5% vs 50%, p = 0.217; a mean difference of 12.5%, 95%CI: -17.5% to 42.5%; and a rate ratio of 1.25, 95%CI: 0.71 to 2.23) and a lower microscopic cure (47.9% vs. 62.5%, p = 0.151; a mean difference of -14.6%, 95%CI: -44.3% to 15.1%; and a rate ratio of 0.77, 95%CI: 0.43 to 1.37). The two groups had comparable times to clinical cure (SER: 3.1 ± 1.8 days, CLO: 3.4 ± 2.7 days; p = 0.848) and substantial satisfaction rates (SER: 66.7%, CLO: 60.4%; p = 0.753). No side effects were reported. Of 60 participants who gave birth at Siriraj Hospital, there were no significant differences in pregnancy outcomes. Repeated SER dosing eradicated symptoms and enhanced the microscopic cure rate. Recurrence was observed in four SER and two CLO participants within 1-2 months. CONCLUSION: In the treatment of acute VC during pregnancy, 300 mg SER and 500 mg CLO exhibited comparable efficacy in terms of clinical and microscopic cure rates, satisfaction, side effects, time to clinical cure, recurrence rates, and pregnancy outcomes. TRIAL REGISTRATION: TCTR20190308004 (registration date March 8, 2019).

VagiBIOM Lactobacillus suppository improves vaginal health index in perimenopausal women with bacterial vaginosis: a randomized control trial.

Bacterial vaginosis (BV) can cause vaginal dysbiosis that may influence general vaginal health and pregnancy complications. Balancing vaginal microbiome using Lactobacillus spp. may be a new way to prevent and treat mild BV. We conducted a randomized, double-blind, placebo-controlled pilot study aimed at evaluating the effect of the product VagiBIOM, a multi-Lactobacillus vaginal suppository, on peri- and premenopausal women with BV in restoring vaginal pH and overall vaginal health by resetting the vaginal microbiome composition. Sixty-six peri- and premenopausal women with BV symptoms were randomized with a 2:1 ratio to be treated with VagiBIOM or placebo suppositories. Vaginal pH, VAS itching score, total Nugent score, and vaginal health index (VHI) were measured. Vaginal microbiome changes before and after the treatment were analyzed by 16S rRNA sequencing and bioinformatics analysis. After 4 weeks of intervention with VagiBIOM or a placebo, the mean score for vaginal pH, VAS itching, and total Nugent score was significantly decreased from the baseline. Compared to the baseline scores, the VHI scores improved significantly following 28-day intervention (p < 0.001). Our results revealed two Lactobacillus species, L. hamsteri, and L. helveticus, as indicator species occurring differentially in the VagiBIOM-treated group. Furthermore, the regression and species network analyses revealed significant bacterial associations after VagiBIOM treatment. Lactobacillus hamsteri was positively associated with the Nugent score and negatively associated with vaginal pH. L. iners and L. salivarius were positively and inversely associated with VHI. As is typical, Bacteroides fragilis was positively associated with vaginal pH and negatively associated with the Nugent score. Interestingly, the Lactobacillus spp. diversity improved after VagiBIOM treatment. The VagiBIOM suppository treatment for peri- and premenopausal women with BV significantly relieved vaginal itching by decreasing vaginal pH and Nugent scores and improving the overall VHI after 4 weeks' intervention. This effect was primarily the result of VagiBIOM improving vaginal Lactobacillus diversity.Trial Registration ClinicalTrials.gov registration: NCT05060029, first registration 09/28/2021: Title: A Pilot Study to Evaluate the Efficacy and Safety of Lactobacillus Species Suppositories on Vaginal Health and pH.

Prophylactic application of vaginal lactic acid bacteria against urogenital pathogens and its prospective use in sanitary suppositories / Aplicación profiláctica de bacterias ácido lácticas vaginales contra patógenos urogenitales y su uso prospectivo en supositorios sanitarios

Beneficial and pathogenic microbes coexist in the vaginal canal, where a diminishing population of lactic acid bacteria may cause recurring urogenital infections. Probiotic bacteria Lactobacillus crispatus, Lactobacillus gasseri, Lactobacillus vaginalis, and pathogenic microbes Enterococcus faecalis, Enterobacter cloacae, Shigella sp., Staphylococcus epidermidis, and Escherichia fergusonii were isolated from vaginal swabs. Lactobacillus sp. and their probiotic culture free supernatant (PCFS) inhibited the growth of the above-mentioned urogenital pathogens. L. crispatus produced both lactic acid and hydrogen peroxide, exhibiting the best antimicrobial potential against the studied pathogens. Lyophilized L. crispatus had a shelf life of 12 months and the lyophilized PCFS also retained its antibacterial property with a minimum inhibition concentration of 1 μg/μL. Carboxy-methyl cellulose-alginate, a green alternative to super-absorbent polymers, was encapsulated with L. crispatus cells. The probiotic in its encapsulated state retained its viability for 21 days, and the bead showed 30% solvent absorptive capacity. PCFS-laced non-woven fabric displayed antibacterial property with no change in its physicochemical properties. These probiotic and postbiotic formulations have excellent prophylactic potential for urogenital infections. Such formulations can be exploited as additives in sanitary suppositories to enhance vaginal health.(AU)

Prophylactic application of vaginal lactic acid bacteria against urogenital pathogens and its prospective use in sanitary suppositories.

Beneficial and pathogenic microbes coexist in the vaginal canal, where a diminishing population of lactic acid bacteria may cause recurring urogenital infections. Probiotic bacteria Lactobacillus crispatus, Lactobacillus gasseri, Lactobacillus vaginalis, and pathogenic microbes Enterococcus faecalis, Enterobacter cloacae, Shigella sp., Staphylococcus epidermidis, and Escherichia fergusonii were isolated from vaginal swabs. Lactobacillus sp. and their probiotic culture free supernatant (PCFS) inhibited the growth of the above-mentioned urogenital pathogens. L. crispatus produced both lactic acid and hydrogen peroxide, exhibiting the best antimicrobial potential against the studied pathogens. Lyophilized L. crispatus had a shelf life of 12 months and the lyophilized PCFS also retained its antibacterial property with a minimum inhibition concentration of 1 µg/µL. Carboxy-methyl cellulose-alginate, a green alternative to super-absorbent polymers, was encapsulated with L. crispatus cells. The probiotic in its encapsulated state retained its viability for 21 days, and the bead showed 30% solvent absorptive capacity. PCFS-laced non-woven fabric displayed antibacterial property with no change in its physicochemical properties. These probiotic and postbiotic formulations have excellent prophylactic potential for urogenital infections. Such formulations can be exploited as additives in sanitary suppositories to enhance vaginal health.

3D-printed prednisolone phosphate suppositories with tunable dose and rapid release for the treatment of inflammatory bowel disease.

Established medicines are often not tailored to the needs of the pediatric population, causing difficulties with administration or dosing. Three-dimensional (3D) printing technology allows novel approaches for compounding of personalized medicine, as is exemplified in this study for the automated compounding of rectal preparations for children. We investigated the material requirements to print prednisolone phosphate-loaded suppositories with tunable dose and rapid drug release for the treatment of inflammatory bowel diseases. Three formulations containing 4 % w/w prednisolone sodium phosphate (PSP) and different amounts of hydroxypropyl cellulose (HPC) and mannitol as excipients were printed as suppositories with a fused deposition modeling (FDM) 3D-printer. Dissolution studies showed that the PSP release rate was increased when higher weight fractions of mannitol were added as a pore former, with 90 % drug release within 30 min for mannitol 48 % w/w. We further printed suppositories with 48 % mannitol with different infill densities and dimensions to tune the dose. Our findings demonstrated that 3D-printed suppositories with PSP doses ranging from 6 to 30 mg could be compounded without notably affecting the dissolution kinetics, ensuring equivalent therapeutic efficacies for different doses.

[Onto-phylogenetic prerequisites for development of chronic cystitis in women].

INTRODUCTION: Urinary tract infections (UTIs) are among the most common bacterial infections. At the request "cystitis", there are 12,067 publications in the RSCI system (e.library) as of 10/08/2023 and 16,332 articles were screened in the Pubmed. This is evidence that the problem of cystitis is far from being resolved. MATERIAL AND METHODS: A total of 425 patients with bacterial vaginosis and 77 women with chronic recurrent cystitis were included in the study. In all patients, the vaginal biocenosis was assessed through molecular genetic testing. The examination included filling out the Russian version of the Acute Cystitis Symptom Score (ACSS), urinalysis, and urine culture. In addition, local microcirculation was measured using laser Doppler flowmetry (LDF). After examination, patients were prescribed basic therapy and randomly assigned to one of three groups. In a control group (n=17), only basic therapy, consisting of fosfomycin 3.0 once at night + furagin 100 mg after meals 3 times a day for 5 days was prescribed. In the main group 1, 29 women received basic therapy plus Superlymph suppositories 10 units 2 times a day vaginally for 10 days. In the main group 2, 31 patients received basic therapy plus suppositories Superlymph 10 units (rectally in the morning) and Acylact Duo (vaginally in the evening) for 10 days. RESULTS: Among 425 patients with bacterial vaginosis, 78 (18.3%) complained of various urinary disorders, but only 21 women (4.9% of those with vaginal dysbiosis and 26.9% with dysuria) had a diagnosis of cystitis. In all cases, it was an exacerbation of a chronic disease. Among 77 patients with chronic cystitis, normal vaginal flora was initially present in 32 patients (41.6%), and bacterial vaginosis was found in 45 (58.4%) cases. After therapy, positive results were noted in patients of all groups. Complete eradication of the pathogen occurred in 15 women (88.2%) who received only basic therapy; in the main groups 1 and 2, uropathogens were not detected in 27 (93.1%) and 28 (90.3%) cases, respectively. In the control group, the proportion of patients with normal vaginal flora remained virtually unchanged (41.2% [n=7] vs. 47.1% [n=8]). In the main group 1, the proportion of patients with normal vaginal flora almost doubled: from 41.4% (n=12) to 79.3% (n=23). In main group 2, restoration of vaginal flora was noted in 87.1% of cases. CONCLUSION: According to our data, only 4.9% of patients with bacterial vaginosis were diagnosed with chronic cystitis, however, 58.4% of patients with chronic cystitis had vaginal dysbiosis. The use of a complex of antimicrobial peptides and cytokines has significantly increased the bidirectional effect of therapy. Suppositories Superlymph in a combination with vaginal use of Acylact Duo allow to obtain the best results.

A phase I study of intra-anal artesunate (suppositories) to treat anal high-grade squamous intraepithelial lesions.

BACKGROUND: Ablation or surgical excision is the typical treatment of anal high-grade squamous intraepithelial lesions (HSIL). Recurrences are common due to the persistence of underlying human papillomavirus (HPV) infection. Additional well-tolerated and effective non-surgical options for HPV-associated anal disease are needed. METHODS: This 3+3 dose escalation Phase I clinical trial evaluated the safety and tolerability of artesunate suppositories in the treatment of patients with biopsy-proven HSIL. RESULTS: The maximal tolerated dose was 400 mg, administered in 3 cycles. All adverse events associated with the use 200- and 400-mg artesunate suppositories were Grade 1. At the 600-mg dose, patients experienced clinically significant nausea. CONCLUSION: Artesunate suppositories are a safe treatment option for anal HSIL.

Rectal artesunate suppositories for the pre-referral treatment of suspected severe malaria.

In this Policy Forum article, James A. Watson and colleagues discuss recent guidelines relating to pre-referral treatment of suspected severe malaria with rectal artesunate suppositories in remote areas.

Can vaginal lactobacillus suppositories help reduce urinary tract infections?

INTRODUCTION AND HYPOTHESIS: Recurrent urinary tract infections (rUTIs) are a burden to patients and the health care economy. Vaginal probiotics and supplements have gained significant attention in mainstream media and lay press as a non-antibiotic alternative. We performed a systematic review to determine whether vaginal probiotics are an effective means of prophylaxis for rUTI. METHODS: A PubMed/MEDLINE article search was performed from inception to August 2022 for prospective, in vivo use of vaginal suppositories for the prevention of rUTIs. Search terms included: vaginal probiotic suppository (34 results), vaginal probiotic randomized (184 results), vaginal probiotic prevention (441 results), vaginal probiotic UTI (21 results), and vaginal probiotic urinary tract infection (91 results). A total of 771 article titles and abstracts were screened. RESULTS: A total of 8 articles fit the inclusion criteria and were reviewed and summarized. Four were randomized controlled trials, with 3 of the studies having a placebo arm. Three were prospective cohort studies, and 1 was a single arm, open label trial. Five of the 7 articles that specifically evaluated for rUTI reduction with vaginal suppositories did find a decreased incidence with probiotic use; however, only 2 had statistically significant results. Both of these were studies of Lactobacillus crispatus and were not randomized. Three studies demonstrated the efficacy and safety of Lactobacillus as a vaginal suppository. CONCLUSION: Current data support the use of vaginal suppositories containing Lactobacillus as a safe, non-antibiotic measure, but actual reduction of rUTI in susceptible women remains inconclusive. The appropriate dosing and duration of therapy remain unknown.

Mesalazine hollow suppositories based on 3D printing for treatment of ulcerative colitis.

Mesalazine (MSZ) suppositories are a first-line medication for the localized treatment of ulcerative colitis (UC). However, the frequent defecation of patients with UC influences the retention of the suppository in the rectum and multiple doses have to be applied. Here, a mesalazine hollow suppository (MHS) is developed using three-dimensional (3D) printing. The MHS is composed of an inner supporting spring and an outer MSZ-loaded curved hollow shell. Springs were prepared using fused deposition modeling (FDM) 3D printing with thermoplastic urethane filaments, followed by splitting. The optimal parameters, including elasticity, filament diameter, spring inner diameter, and filament distance, were screened. The shell was prepared by FDM 3D printing utilizing MSZ, polyvinyl alcohol, and polyethylene glycol, which were assembled with springs to obtain FDM 3D-printed MHS (F-MHS); if 3D-printed metal molding was used in preparing shell, mold-formed MHS (M-MHS) was obtained. The F-MHS exhibited faster MSZ release than the M-MHS; therefore, the molding method is preferable. The inserted M-MHS was retained in the rat rectum for 5 h without affecting defecation. M-MHS alleviated tissue damage of UC rats and reduced inflammation with low levels of myeloperoxidase and proinflammatory cytokines. Personalized MHS is a promising medication for the localized treatment of UC.

[Chronic cystitis: how to prolong the relapse-free period?]

INTRODUCTION: Chronic cystitis predominates in the structure of urinary tract infections (UTIs). International guidelines are mainly focused on the treatment of acute uncomplicated cystitis; the approaches for managing patients with chronic cystitis has not been sufficiently developed. MATERIAL AND METHODS: A total of 91 patients were included in prospective multicenter randomized comparative controlled study. They were divided into three groups. In the group 1, 32 women received only standard antibiotic therapy for 5 days. In the group 2, 28 patients (received standard therapy plus rectal suppositories Superlymph 25 IU 1 time per day for 10 days). In the main group, 31 women received standard therapy in combination with the use of rectal suppositories Superlymph at a dose of 10 IU 1 time per day for 20 days. Standard antibiotic therapy included fosfomycin trometamol 3.0 g once and furazidin 100 mg three times for 5 days. To assess the long-term results, patients were invited for a follow-up 6 months after the end of therapy. AIM: To determine the long-term results of combined etiologic and pathogenetic therapy, including Superlymph rectal suppositories at a dose of 10 U and 25 U, in patients with chronic cystitis. RESULTS: Six months later, 82/91 (90.1%) women were examined to assess the long-term results. At 6 months, in group 1 a relapse of the cystitis developed in 17 women (60.7%) after an average of 67.3+/-9.4 days. In group 2, recurrence was observed in 12 patients (44.4%), and the relapse-free period was longer, averaging of 84.3+/-9.2 days. The best results were demonstrated in the main group, in which the relapse-free period lasted an average of 123.5+/-8.7 days, and a relapse developed in only 8 cases (29.6%). In 19 patients (70.4%) there were no symptoms after six months. Differences between groups were highly significant (p<0.001). In all groups, none of the patients had more than one recurrence of the cystitis during the follow-up. CONCLUSION: Combined antibiotic therapy results in the absence of recurrence within six months in 39.3% of patients with chronic cystitis. Complex etiologic and pathogenetic therapy, including Superlymph rectal suppositories, allows to significantly reduce the number of recurrences and prolong the relapse-free period. Among the patients who received a course of local cytokine therapy at a dose of 25 units for 10 days, 55.6% did not have a recurrence of chronic cystitis within 6 months. In the group of patients who, along with etiologic therapy, received Superlymph rectal suppositories at a dose of 10 IU for 20 days, a relapse was absent in 70.4% of patients.

[The efficiency of various cytokine therapy regimens in the complex treatment of men with chronic abacterial prostatitis].

INTRODUCTION: Chronic prostatitis (CP) is one of the most important and discussed urological diseases. Treatment of bacterial CP with an established pathogen usually is not associated with any difficulties. Chronic abacterial prostatitis (CAP) remains the most problematic issue. Immune defense mechanisms are important in the development of CP, including a decrease in the functional activity of monocytes/ macrophages, neutrophils, as well as imbalance of pro- and anti-inflammatory cytokines. AIM: To evaluate the efficiency of various schemes of using the immunomodulatory drug Superlymph as part of the combination therapy of men with CAP. MATERIALS AND METHODS: A total of 90 patients with category IIIa CAP (NIH, 1995) were included in the study. In the control group, patients received basic therapy of CAP, namely behavioral therapy, 1-adrenoblocker and fluoroquinolone for 28 days. In the main group I basic therapy in combination with Superlymph 25 ME in one suppository q.d. for 20 days was administered. In the main group II basic therapy in combination with Superlymph 10 ME in one suppository b.i.d. for 20 days was given. Evaluation of treatment efficiency was carried out after 14 +/- 2 days (visit 2) and 28+/- 2 days (visit 3) from the start of treatment. RESULTS: The study groups were homogeneous, and baseline characteristics did not differ significantly (p>0.05). However, significant differences were found between the results in the main groups and the control group at visit 2 for all the indicators (p<0.05). The number of daytime urinations was lower in the main group I and II compared to CG by 16.7% and 28.4%, the number of night urination by 28% and 40%, the average IPSS score by 29.1% and 38.3%, the average QoL score by 32.4% and 45.9%, the average NIH-CPSI score by 26.8% and 37.4%, the number of leukocytes in expressed prostatic secretion by 41.2% and 52.1%, prostate volume by 16.8% and 21.8%, bladder volume by 15.8% and 21.7%, and Qmax by 14.3% and 21.2%, respectively. Similar significant differences between the main groups and control group were also seen at visit 3, while the indicators in main groups I and II reached normal values after 28 days of therapy. In this study, for the first time, a comparative analysis of two different treatment regimens with Superlymph was carried out. In the main group I, patients received suppositories at a dose of 25ME q.d., while in the main group II, the drug was administered 10 ME b.i.d. The results indicate a comparable efficiency of both schemes after 4 weeks. However, in the main group II, after 2 weeks, there was a significantly more pronounced positive dynamics of all indicators in comparison with the main group I (p<0.05). Consequently, the use of Superlymph at a dose of 10ME b.i.d. a day allows to reduce the severity of the inflammatory process in a shorter time. CONCLUSION: The use of Superlymph in patients with CAP allows to reduce the severity of clinical manifestations in a shorter time, and has a positive effect on the dynamics of the inflammatory process, which leads to an improvement in the quality of life. According to our results, the most effective scheme in patients with CAP is basic therapy in combination with Superlymph 10 ME for 1 suppository 2 times a day for 10 days. In our opinion, Superlymph can be effectively used as part of the combination therapy of men with CAP.

[Spermoprotective properties of Prostatex in patients with chronic abacterial prostatitis].

AIM: To study the effect of Prostatex therapy on spermatogenesis in patients with infertility that developed due to chronic abacterial prostatitis. MATERIALS AND METHODS: A total of 60 men with infertility in marriage and chronic abacterial prostatitis were included in the study. All patients received therapy with Prostatex rectal suppositories 10 mg 1 time per day. The duration of treatment was 30 days. After taking the drug, patients were observed for 50 days. The study was carried out for 80 days and included 3 visits at 1, 30 and 80 days. The study showed that the use of Prostatex rectal suppositories 10 mg had a positive effect on the main indicators of spermatogenesis, as well as on the subjective and objective symptoms of chronic abacterial prostatitis. Based on these results, we recommend Prostatex rectal suppositories to patients with chronic abacterial prostatitis, accompanied by impaired spermatogenesis, according to the scheme: 1 suppository 10 mg 1 time per day for 30 days.

Effects of topical dehydroepiandrosterone therapy in women after pelvic organ prolapse surgery.

OBJECTIVE: Pelvic organ prolapse (POP) occurs predominantly in postmenopausal women. Restoration of the proper estrogenization of vaginal mucosa is important in preoperative and postoperative treatment, increasing the effectiveness of this approach. The objective of this study was the development of intravaginal vaginal suppositories containing DHEA and comparison of the clinical effects of vaginal topical therapy with DHEA, estradiol, or antibiotic after POP surgery. METHOD: Nine types of vaginal suppositories containing 6.5 mg DHEA in different bases were prepared to find optimal formulation for the vaginal conditions. Ninety women referred for POP surgery were randomly assigned to one of three groups receiving topical treatment in the postoperative period (estradiol, DHEA, or antibiotic). On admission to hospital and during follow-up vaginal pH, vaginal maturation index and vaginal symptoms were assessed. RESULTS: Vaginal suppositories with the base made from polyethylene glycol 1,000 without surfactants characterized the highest percentage of the released DHEA. In women treated with topical estradiol or DHEA a significant decrease in the number of parabasal cells, increase in superficial and intermediate cells in the vaginal smears, decrease in vaginal pH, and reduction of vaginal symptoms were observed. CONCLUSIONS: The use of topical therapy with DHEA or the use of topical therapy with estradiol in the postoperative period were both shown to improve maturation index, vaginal pH, and vaginal symptoms. The benefits of topical therapy with DHEA after pelvic organ prolapse repair brings similar results as estradiol, without potential systemic exposure to increased concentrations of sex steroids above levels observed in postmenopausal women.

Development of optimal in vitro release and permeation testing method for rectal suppositories.

Currently there are no compendial assays for testing drug release from rectal suppositories. It is therefore essential to study different in vitro release testing (IVRT) and in vitro permeation testing (IVPT) methods for identifying a suitable technique to compare in vitro drug release and to predict in vivo performance of rectal suppositories. In the present study, three different rectal suppository formulations of mesalamine (CANASA, Generic, and In-house) were studied for in vitro bioequivalence. All the different suppository products were characterized by performing weight variation, content uniformity, hardness, melting time, and pH tests. Viscoelastic behavior of the suppositories was also tested both in presence and absence of mucin. Four different IVRT techniques such as Dialysis, Horizontal Ussing Chamber, Vertical Franz cell, and USP apparatus 4. IVPT studies were performed using Horizontal Ussing chamber and Vertical Franz cell methods. Q1/Q2 equivalent products (CANASA, Generic) and a half-strength product were studied to understand the reproducibility, bio relevance, and discriminatory ability of the IVRT and IVPT methods. This study is the first of its kind where molecular docking studies were performed to determine the potential interactions of drug (mesalamine) with mucin, IVRT studies were conducted with and without the presence of mucin, and porcine rectal mucosa was used to perform IVPT tests. The USP 4 method and Horizontal Ussing chamber methods were found to be suitable IVRT and IVPT techniques, respectfully, for rectal suppositories. RLD (Reference Listed Drug) and Generic rectal suppositories were found to exhibit similar release rate and permeation profiles obtained from USP 4, and the IVPT studies, respectfully. Wilcoxon Rank Sum/Mann-Whitney rank test, conducted for the IVRT profiles obtained using USP 4 method, proved the sameness of RLD and Generic suppository products.

Improving Bowel Management in Children With Spina Bifida.

OBJECTIVES: In individuals with spina bifida (SB), bowel incontinence is associated with lower quality of life and lower likelihood of employment. In an effort to maximize bowel continence in children and adolescents, we created a bowel management assessment and follow-up protocol in a multidisciplinary clinic. Here we report the results of this protocol using quality-improvement methodology. METHODS: Continence was defined as no unplanned bowel movements. Our protocol involved: (1) a standardized 4-item questionnaire about bowel continence and consistency; (2) if the patient was not achieving continence, an intervention starting with oral medication (stimulant and/or osmotic laxatives), and/or suppositories (glycerin or bisacodyl) followed by an escalation to trans-anal irrigation, or continence surgery; and (3) follow-up phone calls at regular intervals to monitor progress and make changes as needed. Results are summarized with descriptive statistics. RESULTS: We screened 178 eligible patients in the SB clinic. Eighty-eight agreed to participate in the bowel management program. Of those who did not participate, the majority (68/90, 76%) were already achieving continence with their bowel regimen. Of children in the program, most (68/88, 77%) had a diagnosis of meningomyelocoele. At 1 year, the proportion of patients who were bowel accident free improved to 46% (vs 22% initially, P = 0.0007). CONCLUSIONS: A standardized bowel management protocol, primarily the use of suppositories and trans-anal irrigation to achieve social continence, as well as frequent telephone follow-up, can reduce bowel incontinence in children and adolescents with SB.

Pharmacokinetic and metabolite profile of orally administered anemoside B4 in rats with an improved exposure in formulations of rectal suppository.

ETHNOPHARMACOLOGICAL RELEVANCE: Pulsatilla chinensis (Bunge) Regel is a traditional Chinese herbal medicine used to treat intestinal amebiasis, malaria, vaginal trichomoniasis, and bacterial infections. Anemoside B4 (AB4), a pentacyclic triterpenoid saponin, is one of the primary bioactive substances in Pulsatilla chinensis (Bunge) Regel, and gavage administration of AB4 to animals has been demonstrated to exhibit anticancer, anti-inflammatory, and antiviral actions. However, AB4 exposure in plasma is very low after oral administration, and the biotransformation of AB4 in vivo after oral administration remains unknown. AIM OF THE STUDY: The reason for conducting this research was to explore at the metabolite profile of AB4 in rats following oral administration. Additionally, we aimed to develop an appropriate extravascular formulation to increase the exposure and duration of AB4 in vivo. MATERIALS AND METHODS: A well-validated HPLC-QQQ-MS/MS method was used for the quantification of AB4 in plasma and was further applied to evaluate and compare the pharmacokinetic properties of AB4 dissolved in a saline solution and AB4 formulations in a rectal suppository or enteric capsule. Reliable UHPLC coupled to Q-Exactive Plus high-resolution MS was used to identify the metabolites in rat plasma, bile, urine, and faeces. RESULTS: AB4 was extensively metabolized, and a total of 29 metabolites were identified. The primary metabolic routes included deglycosylation, oxidation, dehydrogenation, reduction, sulfation, hydration, acetylation, and glucuronidation. The pharmacokinetic comparison showed that both the rectal suppository and enteric capsule increased the exposures of AB4 and one of its active metabolites, 23-hydroxybetulinic acid (23-HA). Notably, rectal suppositories increased systemic AB4 exposure (AUC0-∞) by approximately 49 and 28 times higher than that of the AB4 saline solution and enteric capsules, respectively. The t1/2 of AB4 was extended to approximately 7 h after rectal administration compared to 2 h after oral administration. CONCLUSION: Overall, our study demonstrated that the mismatched exposure-response relationship of AB4 could result from extensive metabolism in the gastrointestinal and circulatory systems. Thus, a rectal suppository could be an alternative formulation of AB4 to obtain both higher and longer exposure.

The efficacy of glycerin suppositories for preterm infants: A meta-analysis of randomized controlled studies.

BACKGROUND: The effect of glycerin suppositories on full enteral feeds remained controversial in preterm infants, and thus we conducted this meta-analysis to identify the influence of glycerin suppositories on full enteral feeds in preterm infants. METHODS: The protocol was registered in PROSPERO (CRD20214283090). We searched PubMed, EMbase, Web of science, EBSCO and Cochrane library databases through February 2020, and included randomized controlled trials assessing the effect of glycerin suppositories on full enteral feeds in preterm infants. This meta-analysis was performed using the random-effect model. RESULTS: Six Randomized controlled trials were included in the meta-analysis. Overall, compared with control group in preterm infants, glycerin suppositories demonstrated no significant effect on days to full enteral feeds (mean difference = -0.26; 95% confidence interval [CI] = -1.16 to 0.65; P = .58), the incidence of necrotizing enterocolitis (odd ratio = 3.62; 95% CI = 0.56-23.32; P = .18) or death (odd ratio = 1.46; 95% CI = 0.40-5.40; P = .57), but may increase the days under phototherapy (mean difference = 0.50; 95% CI = 0.43-0.57; P < .00001). Only low heterogeneity was seen among all outcomes. CONCLUSIONS: Glycerin suppositories may provide no additional benefits to preterm infants.

A randomized trial of safety, acceptability and adherence of three rectal microbicide placebo formulations among young sexual and gender minorities who engage in receptive anal intercourse (MTN-035).

Efforts to develop a range of HIV prevention products that can serve as behaviorally congruent viable alternatives to consistent condom use and oral pre-exposure prophylaxis (PrEP) remain crucial. MTN-035 was a randomized crossover trial seeking to evaluate the safety, acceptability, and adherence to three placebo modalities (insert, suppository, enema) prior to receptive anal intercourse (RAI). If participants had no RAI in a week, they were asked to use their assigned product without sex. We hypothesized that the modalities would be acceptable and safe for use prior to RAI, and that participants would report high adherence given their behavioral congruence with cleansing practices (e.g., douches and/or enemas) and their existing use to deliver medications (e.g., suppositories; fast-dissolving inserts) via the rectum. Participants (N = 217) were sexual and gender minorities enrolled in five different countries (Malawi, Peru, South Africa, Thailand, and the United States of America). Mean age was 24.9 years (range 18-35 years). 204 adverse events were reported by 98 participants (45.2%); 37 (18.1%) were deemed related to the study products. The proportion of participants reporting "high acceptability" was 72% (95%CI: 65% - 78%) for inserts, 66% (95%CI: 59% - 73%) for suppositories, and 73% (95%CI: 66% - 79%) for enemas. The proportion of participants reporting fully adherent per protocol (i.e., at least one use per week) was 75% (95%CI: 69% - 81%) for inserts, 74% (95%CI: 68% - 80%) for suppositories, and 83% (95%CI: 77% - 88%) for enemas. Participants fully adherent per RAI-act was similar among the three products: insert (n = 99; 58.9%), suppository (n = 101; 58.0%) and enema (n = 107; 58.8%). The efficacy and effectiveness of emerging HIV prevention drug depends on safe and acceptable delivery modalities that are easy to use consistently. Our findings demonstrate the safety and acceptability of, and adherence to, enemas, inserts, and suppositories as potential modalities through which to deliver a rectal microbicide.