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Medicine Oct 2020100 mg rectal nonsteroidal anti-inflammatory drugs (NSAIDs) and pancreatic stents both significantly reduce the incidence of post-endoscopic retrograde... (Meta-Analysis)
Meta-Analysis
Rectal nonsteroidal anti-inflammatory drugs and pancreatic stents in preventing post-endoscopic retrograde cholangiopancreatography pancreatitis in high-risk patients: A network meta-analysis.
BACKGROUND
100 mg rectal nonsteroidal anti-inflammatory drugs (NSAIDs) and pancreatic stents both significantly reduce the incidence of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. Direct comparison of randomized controlled trials (RCTs) between them in high-risk patients is absent. We conducted this network meta-analysis to indirectly compare the efficacies of 100 mg rectal NSAIDs and pancreatic stents in preventing post-ERCP pancreatitis (PEP) in high-risk patients and help us decide which is preferred in clinical practice.
METHODS
A comprehensive search was done to identify RCTs published in English full-text. Interventions included 100 mg rectal NSAIDs (diclofenac or indomethacin) and pancreatic stents. Only studies with high-risk patients of PEP were included. Meta-analyses of NSAIDs and pancreatic stents were conducted respectively. A network meta-analysis using the Bayesian method was performed.
RESULTS
We included 14 RCTs, 8 on pancreatic stents and 6 on 100 mg rectal NSAIDs in high-risk patients. There was no direct comparison between them. After excluding an outlier study on NSAIDs (n = 144), meta-analyses showed they both significantly and statistically reduced the incidence of PEP in high-risk patients (pancreatic stents: n = 8 studies, random-effects risk ratio (RR)0.41, 95%CI 0.30-0.56, I = 0%; NSAIDs: n = 5 studies, random-effects RR 0.37, 95%CI 0.25-0.54, I = 0%). And network meta-analysis showed efficacy of 100 mg rectal NSAIDs was equal to pancreatic stents (random-effects RR 0.94, 95%CI 0.50-1.8).
CONCLUSIONS
The efficacy of 100 mg rectal NSAIDs (diclofenac or indomethacin) seems equally significant to pancreatic stents in preventing PEP in high-risk patients. Considering the cost-effectiveness and safety, 100 mg diclofenac or indomethacin may be preferred.
Topics: Administration, Rectal; Anti-Inflammatory Agents, Non-Steroidal; Cholangiopancreatography, Endoscopic Retrograde; Humans; Pancreatitis; Postoperative Complications; Randomized Controlled Trials as Topic; Risk Factors; Stents
PubMed: 33080710
DOI: 10.1097/MD.0000000000022672 -
Advanced Drug Delivery Reviews Jun 2014The rectal route can be considered a good alternative to the oral route for the paediatric population because these dosage forms are neither to be swallowed nor need to... (Review)
Review
The rectal route can be considered a good alternative to the oral route for the paediatric population because these dosage forms are neither to be swallowed nor need to be taste-masked. Rectal forms can also be administered in an emergency to unconscious or vomiting children. Their manufacturing cost is low with excipients generally regarded as safe. Some new formulation strategies, including mucoadhesive gels and suppositories, were introduced to increase patient acceptability. Even if recent paediatric clinical studies have demonstrated the equivalence of the rectal route with others, in order to enable the use of this promising route for the treatment of children in the 21st Century, some effort should be focused on informing and educating parents and care givers. This review is the first ever to address all the aforementioned items, and to list all drugs used in paediatric rectal forms in literature and marketed products in developed countries.
Topics: Administration, Rectal; Child; Humans; Pediatrics; Pharmaceutical Preparations
PubMed: 24871671
DOI: 10.1016/j.addr.2014.05.012 -
BMC Infectious Diseases Mar 2008Rectal administration of artemisinin derivatives has potential for early treatment for severe malaria in remote settings where injectable antimalarial therapy may not be... (Comparative Study)
Comparative Study Review
BACKGROUND
Rectal administration of artemisinin derivatives has potential for early treatment for severe malaria in remote settings where injectable antimalarial therapy may not be feasible. Preparations available include artesunate, artemisinin, artemether and dihydroartemisinin. However each may have different pharmacokinetic properties and more information is needed to determine optimal dose and comparative efficacy with each another and with conventional parenteral treatments for severe malaria.
METHODS
Individual patient data from 1167 patients in 15 clinical trials of rectal artemisinin derivative therapy (artesunate, artemisinin and artemether) were pooled in order to compare the rapidity of clearance of Plasmodium falciparum parasitaemia and the incidence of reported adverse events with each treatment. Data from patients who received comparator treatment (parenteral artemisinin derivative or quinine) were also included. Primary endpoints included percentage reductions in parasitaemia at 12 and 24 hours. A parasite reduction of >90% at 24 hours was defined as parasitological success.
RESULTS
Artemisinin and artesunate treatment cleared parasites more rapidly than parenteral quinine during the first 24 hours of treatment. A single higher dose of rectal artesunate treatment was five times more likely to achieve >90% parasite reductions at 24 hours than were multiple lower doses of rectal artesunate, or a single lower dose administration of rectal artemether.
CONCLUSION
Artemisinin and artesunate suppositories rapidly eliminate parasites and appear to be safe. There are less data on artemether and dihydroartemisinin suppositories. The more rapid parasite clearance of single high-dose regimens suggests that achieving immediate high drug concentrations may be the optimal strategy.
Topics: Administration, Rectal; Adolescent; Adult; Aged; Aged, 80 and over; Animals; Antimalarials; Artemisinins; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Malaria; Middle Aged; Parasitemia; Plasmodium falciparum
PubMed: 18373841
DOI: 10.1186/1471-2334-8-39 -
BMC Gastroenterology Mar 2017Acute pancreatitis is a severe complication of endoscopic retrograde cholangiopancreatography (ERCP). Previous meta-analyses have shown that indomethacin effectively... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acute pancreatitis is a severe complication of endoscopic retrograde cholangiopancreatography (ERCP). Previous meta-analyses have shown that indomethacin effectively prevents this complication; however, the data are limited. We performed a systematic review and meta-analysis to clarify the applications for rectal indomethacin.
METHODS
A systematic search was performed in June 2016. Human prospective, randomized, placebo-controlled trials that compared rectally administered indomethacin with a placebo for the prevention of post-ERCP pancreatitis (PEP) were included. A meta-analysis was performed using a random-effects model to assess the outcomes (PEP) using Review Manager 5.0.
RESULTS
Seven randomized controlled trials met the inclusion criteria (n = 3013). The overall incidence of PEP was significantly lower after prophylactic administration of rectal indomethacin than after administration of the placebo (RR, 0.58, 95% CI, 0.40-0.83; P = 0.004). A subgroup analysis was performed for rectal indomethacin administration compared to a placebo in high-risk patients (RR, 0.46; 95% CI, 0.32-0.65; P < 0.00001) and average-risk patients (RR, 0.75; 95% CI, 0.46-1.22; P = 0.25) and for administration before ERCP (RR, 0.56; 95% CI, 0.39-0.79; P = 0.001) and after the procedure (RR, 0.61; 95% CI, 0.26-1.44; P = 0.26).
CONCLUSIONS
This meta-analysis indicated that prophylactic rectal indomethacin is not suitable for all patients undergoing ERCP but it is safe and effective to prevent PEP in high-risk patients. In addition, rectal indomethacin administration before ERCP is superior to its administration after ERCP for the prevention of PEP.
Topics: Acute Disease; Administration, Rectal; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Cholangiopancreatography, Endoscopic Retrograde; Female; Humans; Indomethacin; Male; Middle Aged; Pancreatitis; Patient Selection; Premedication; Randomized Controlled Trials as Topic; Risk Factors
PubMed: 28298192
DOI: 10.1186/s12876-017-0599-4 -
A Mechanistic In Vivo/Ex Vivo Pharmacokinetic-Pharmacodynamic Model of Tenofovir for HIV Prevention.CPT: Pharmacometrics & Systems... Mar 2021Defining tissue and plasma-specific prophylactic drug concentrations is central to pre-exposure prophylaxis product development for sexual transmission of HIV-1.... (Clinical Trial)
Clinical Trial Comparative Study
Defining tissue and plasma-specific prophylactic drug concentrations is central to pre-exposure prophylaxis product development for sexual transmission of HIV-1. Pharmacokinetic (PK) data from study RMP-02/MTN-006 comparing single dose oral tenofovir disoproxil fumarate with single and multiple dose rectal tenofovir (TFV) gel administration in HIV-1 seronegative adults was used to construct a multicompartment plasma-rectal tissue population PK model for TFV and tenofovir-diphosphate (TFVdp) in plasma and rectal tissue. PK data were collected in five matrices: TFV (plasma, rectal tissue homogenate), TFVdp (peripheral blood mononuclear cells, rectal mononuclear cells (MMCs), rectal tissue homogenate). A viral growth compartment and a delayed effect compartment for p24 antigen expression measured from an ex vivo explant assay described HIV-1 infection and replication. Using a linear PK/pharmacodynamic model, MMC TFVdp levels over 9,000 fmol/million cells in the explant assay provided apparent viral replication suppression down to 1%. Parameters were estimated using NONMEM version 7.4.
Topics: Administration, Oral; Administration, Rectal; Adult; Aged; Anti-HIV Agents; Biological Availability; Drug Development; Female; Gels; HIV Core Protein p24; HIV Infections; HIV Seronegativity; Humans; Leukocytes, Mononuclear; Male; Middle Aged; Models, Theoretical; Pre-Exposure Prophylaxis; Rectum; Tenofovir; Virus Replication
PubMed: 33547874
DOI: 10.1002/psp4.12583 -
Irinotecan-encapsulated double-reverse thermosensitive nanocarrier system for rectal administration.Drug Delivery Nov 2017Intravenously administered for the treatment of rectum cancer, irinotecan produces severe side effects due to very high plasma concentrations. A novel...
Intravenously administered for the treatment of rectum cancer, irinotecan produces severe side effects due to very high plasma concentrations. A novel irinotecan-encapsulated double reverse thermosensitive nanocarrier system (DRTN) for rectal administration was developed as an alternative. The DRTN was fabricated by dispersing the thermosensitive irinotecan-encapsulated solid lipid nanoparticles (SLN) in the thermosensitive poloxamer solution. Its gel properties, pharmacokinetics, morphology, anticancer activity and immunohistopathology were assessed after its rectal administration to rats and tumor-bearing mice. In the DRTN, the solid form of the SLN and the liquid form of the poloxamer solution persisted at 25 °C; the former melted to liquid, and the latter altered to gel at 36.5 °C. The DRTN was easily administered to the anus, gelling rapidly and strongly after rectal administration. Compared to the conventional hydrogel and intravenously administered solution, it retarded dissolution and initial plasma concentration. The DRTN gave sustained release and nearly constant plasma concentrations of irinotecan at 1-3 h in rats, resulting in improved anticancer activity. It induced no damage to the rat rectum and no body weight loss in tumor-bearing mice. Thus, this irinotecan-encapsulated DRTN associated with a reduced burst effect, lack of toxicity and excellent antitumor efficacy would be strongly recommended as a rectal pharmaceutical product alternative to commercial intravenous injection in the treatment of rectum and colon cancer.
Topics: Administration, Intravenous; Administration, Rectal; Animals; Antineoplastic Agents, Phytogenic; Camptothecin; Carcinoma, Squamous Cell; Delayed-Action Preparations; Drug Carriers; Drug Compounding; Female; Humans; Hydrogels; Irinotecan; Lipids; Male; Mice, Nude; Nanomedicine; Nanoparticles; Phase Transition; Poloxamer; Rats, Sprague-Dawley; Solubility; Technology, Pharmaceutical; Transition Temperature; Tumor Burden; Xenograft Model Antitumor Assays
PubMed: 28181835
DOI: 10.1080/10717544.2016.1272651 -
International Journal of Colorectal... May 2024A high number of topical products are available for the treatment of hemorrhoidal symptoms. Sucralfate-based topical products constitute a new treatment alternative that... (Observational Study)
Observational Study
BACKGROUND AND AIMS
A high number of topical products are available for the treatment of hemorrhoidal symptoms. Sucralfate-based topical products constitute a new treatment alternative that act as a mechanical barrier to facilitate healing. The aim of this prospective, observational study was to determine patient- and physician-assessed effectiveness and tolerability of rectal ointment and suppositories containing sucralfate for the treatment of hemorrhoidal symptoms in routine clinical practice.
METHODS
Adult patients with diagnosed, mild-to-moderate, symptomatic non-bleeding hemorrhoids treated with rectal ointment or suppositories containing sucralfate were enrolled. Patients were administered treatment twice per day for at least 1 week until symptom resolution and/or for a maximum of 4 weeks. The primary endpoint was patient-assessed effectiveness on a modified Symptom Severity Score (mSSS, range 0 to 14). Physician-assessed effectiveness (9 symptoms, 0 to 5 Likert scale), hemorrhoid grade, and patient satisfaction were also determined.
RESULTS
Five investigators enrolled 60 patients; mean age was 48.4 ± 16.6 years and 72.4% were female. Pain or pressure sensitivity was reported as the most severe symptom by patients, and pressure sensitivity, discharge, soiling, and prolapse by physicians. Mean patient-assessed mSSS at baseline was 6.6 ± 1.9 and was significantly improved overall and in the ointment and suppository groups individually by -4.6 ± 2.0, -4.4 ± 1.8, and -4.8 ± 2.2, respectively (p < 0.0001). Investigator-assessed mean baseline symptom score was 18.1 ± 3.9 and improved by -7.1 ± 4.5, -6.9 ± 5.4, and -7.3 ± 3.5, respectively (p < 0.0001). Investigator-assessed symptoms of pressure sensitivity, swelling, and discharge were improved to the greatest extent. Hemorrhoid grade was improved in 38% of patients at the end of treatment. Compliance with treatment was 97.4% and patient satisfaction with application and onset of action was high (81.3% and 76.2%, respectively). Both the ointment and suppository were well tolerated.
CONCLUSIONS
The effectiveness of topical ointment or suppository containing sucralfate on patient- and investigator-assessed hemorrhoidal symptoms in real-life clinical practice was demonstrated. Patient satisfaction was high and treatments were well tolerated. Larger controlled trials are warranted to confirm the results.
Topics: Humans; Sucralfate; Hemorrhoids; Female; Suppositories; Male; Middle Aged; Ointments; Prospective Studies; Treatment Outcome; Patient Satisfaction; Adult; Aged; Administration, Rectal
PubMed: 38750150
DOI: 10.1007/s00384-024-04642-7 -
The Korean Journal of Internal Medicine May 2020Acute pancreatitis is the most common and feared adverse event associated with performance of endoscopic retrograde cholangiopancreatography (ERCP). Unremitting effort... (Review)
Review
Acute pancreatitis is the most common and feared adverse event associated with performance of endoscopic retrograde cholangiopancreatography (ERCP). Unremitting effort has been made for over 40 years to minimize the frequency and severity of this complication. Recently, the use of rectal non-steroidal anti-inflammatory drugs (NSAIDs) have opened a new era for its prevention. This review focuses on the role of NSAIDs in pancreatitis, the pharmacokinetics of these agents, and summarizes the results of clinical trials with rectal NSAIDs alone and combination regimens in the prevention of post-ERCP pancreatitis.
Topics: Acute Disease; Administration, Rectal; Anti-Inflammatory Agents, Non-Steroidal; Cholangiopancreatography, Endoscopic Retrograde; Humans; Pancreatitis; Pharmaceutical Preparations
PubMed: 32392660
DOI: 10.3904/kjim.2020.069 -
European Journal of Drug Metabolism and... Oct 2020Omeprazole is a proton pump inhibitor that is used in acid suppression therapy in infants. Infants cannot swallow the oral tablets or capsules. Since, infants require a... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND AND OBJECTIVE
Omeprazole is a proton pump inhibitor that is used in acid suppression therapy in infants. Infants cannot swallow the oral tablets or capsules. Since, infants require a non-standard dose of omeprazole, the granules or tablets are often crushed or suspended in water or sodium bicarbonate, which may destroy the enteric coating. In this study we explore the efficacy and pharmacokinetics of rectally administered omeprazole in infants with gastroesophageal reflux disease (GERD) due to esophageal atresia (EA) or congenital diaphragmatic hernia (CDH) and compare these with orally administered omeprazole.
METHODS
Infants (6-12 weeks postnatal and bodyweight > 3 kg) with EA or CDH and GERD were randomized to receive a single dose of 1 mg/kg omeprazole rectally or orally. The primary outcome was the percentage of infants for whom omeprazole was effective according to predefined criteria for 24-h intraesophageal pH. Secondary outcomes were the percentages of time that gastric pH was < 3 or < 4, as well as the pharmacokinetic parameters.
RESULTS
Seventeen infants, 4 with EA and 13 with CDH, were included. The proportion of infants for whom omeprazole was effective was 56% (5 of 9 infants) after rectal administration and 50% (4 of 8 infants) after oral administration. The total reflux time in minutes and percentages and the number of reflux episodes of pH < 4 decreased statistically significantly after both rectal and oral omeprazole administration. Rectal and oral administration of omeprazole resulted in similar serum exposure.
CONCLUSIONS
A single rectal omeprazole dose (1 mg/kg) results in consistent increases in intraesophageal and gastric pH in infants with EA- or CDH-related GERD, similar to an oral dose. Considering the challenges with existing oral formulations, rectal omeprazole presents as an innovative, promising alternative for infants with pathological GERD.
CLINICAL TRIAL REGISTER
ClinicalTrials.gov Identifier: NCT00226044.
Topics: Administration, Oral; Administration, Rectal; Esophageal Atresia; Esophageal pH Monitoring; Female; Gastroesophageal Reflux; Hernias, Diaphragmatic, Congenital; Humans; Infant; Male; Omeprazole; Pilot Projects; Proton Pump Inhibitors; Treatment Outcome
PubMed: 32594305
DOI: 10.1007/s13318-020-00630-8 -
AIDS and Behavior Feb 2018Rectal douching is a common but potentially risky practice among MSM; MSM who douche may be ideal candidates for rectal microbicides as HIV prevention. Herein we...
Rectal douching is a common but potentially risky practice among MSM; MSM who douche may be ideal candidates for rectal microbicides as HIV prevention. Herein we explored rectal douching and its association with condomless receptive anal intercourse (CRAI), group sex, rates of HIV and other STIs, and likelihood to use rectal microbicide gels. We recruited a sample of 580 MSM from a geosocial-networking smartphone application in Paris, France in 2016. Regression models estimated adjusted risk ratios (aRRs) for associations between rectal douche use and (1) engagement in CRAI, (2) group sex, (3) self-reported HIV and STI diagnoses, and (4) likelihood to use rectal microbicide gels for HIV prevention. 54.3% of respondents used a rectal douche or enema in the preceding 3 months. Douching was significantly associated with CRAI (aRR: 1.77), participation in group sex (aRR: 1.42), HIV infection (aRR: 3.40), STI diagnosis (aRR: 1.73), and likelihood to use rectal microbicide gels (aRR: 1.78). Rectal douching is common among MSM, particularly those who practice CRAI, and rectal microbicide gels may be an acceptable mode of HIV prevention for MSM who use rectal douches.
Topics: Administration, Rectal; Adult; Anti-Infective Agents; Enema; France; HIV Infections; Homosexuality, Male; Humans; Male; Rectum; Risk-Taking; Sexual Behavior; Sexually Transmitted Diseases; Therapeutic Irrigation; Young Adult
PubMed: 28766026
DOI: 10.1007/s10461-017-1873-8