[Survey on Patient Satisfaction with the Usability and Formulation of Budesonide Rectal Foam Following a Change in Head and Applicator Shape and Properties].

Budesonide Rectal Foam (BF) was introduced in 2017 and changed in November 2022 upon request, addressing the challenges encountered with liquid rectal formulations indicated for ulcerative colitis (UC). This formulation is an important agent in the treatment of rectal to sigmoid colon lesions in moderate UC. As the characteristics of the formulation of the rectal formulation are thought to influence patient satisfaction, a survey was conducted on the formulation and patient satisfaction among patients who used BF before and after the change. The survey spanned from January 2023 to May 2023. As the primary endpoint, the same patients were evaluated on the Visual Analogue Scale (VAS) for patient satisfaction. Significant variations in formulation usability and patient satisfaction were observed in 20 eligible patients before and after the change (p<0.05). Patient satisfaction with the formulation was strongly correlated with formulation usability, ease of pushing the head, and ease of insertion (r>0.7). The change in packaging was thought to improve the usability of the formulation and patient satisfaction. The formulation's usability and ease of insertion had a clear influence on satisfaction with the rectal formulation.

Effectiveness of preoperative micronized purified flavonoid fraction treatment and sucralfate-based rectal ointment on hemorrhoidal disease: A case-matched analysis.

BACKGROUND: Hemorrhoidal disease (HD) significantly impacts patients' quality of life. This study aimed to evaluate the effectiveness of preoperative treatment with the micronized purified flavonoid fraction (MPFF) and a sucralfate-based rectal ointment in managing HD symptoms and reducing interventions. METHODS: A prospective quasi-experimental study including consecutive cases and controls matched on the basis of sex was performed in a tertiary referral center. Cases received systemic and local therapy for HD, consisting of a rectal ointment containing 3% sucralfate and herbal extracts plus MPFF, in addition to conservative therapy, while controls received conservative therapy alone. The hemorrhoidal disease symptom score (HDSS), the Short Health Scale for HD (SHS-HD) score, and the Vaizey Incontinence Score were used to evaluate symptoms severity and their impact on quality of life and continence. Intervention requirements were assessed at baseline (T0) and after 60 days of treatment (T1). RESULTS: Between January and December 2023, a total of 98 patients were assessed for eligibility. After exclusions, 56 patients were enrolled, with 28 in each group. Significant improvements were observed in HD symptom scores from T0 to T1: the intervention group showed a mean change in HDSS of -9 [95% confidence interval (CI) -10 to -8], and the control group showed no significant change (mean change of 0; 95% CI -1.5 to 0). At T1, a higher proportion of patients in the intervention group underwent less invasive interventions compared with controls (18% versus 11%). Age, treatment group, and baseline symptom severity significantly predicted post-treatment symptom scores. CONCLUSIONS: In our study the preoperative treatment with MPFF and a sucralfate-based rectal ointment demonstrated clinical benefits in managing HD symptoms and reducing interventions. Further prospective trials are warranted to confirm and explore additional therapeutic strategies.

Efficacy and safety of rectal chloral hydrate for pediatric procedural sedation: A systematic review and meta-analysis.

BACKGROUND: To evaluate the efficacy and safety of rectal chloral hydrate (CH) in pediatric procedural sedation. METHODS: Seven electronic databases and 3 clinical trials registry platforms were searched, and the deadline was August 2022. Randomized controlled trials evaluating the efficacy and safety of rectal CH in pediatric procedural sedation were included by 2 reviewers. The extracted outcomes included the success rate of sedation, sedation latency, sedation duration, and adverse events. The Cochrane risk of bias tool was used to assess the risk of bias. The outcomes were analyzed using Review Manager 5.3 software. RESULTS: Forty-four randomized controlled trials with 8007 children were included in the meta-analysis. The success rate of sedation in the rectal CH group was significantly higher than that in the placebo group (risk ratio [RR], 2.60 [95% confidence interval [CI], 1.74-3.89]; P < .01; RR, 1.24 [95% CI, 1.01-1.54]; P = .04), oral CH group (RR, 1.12 [95% CI, 1.09-1.14]; I2 = 36%; P < .001; number needed to treat [NNT] = 10), diazepam group (RR, 1.21 [95% CI, 1.10-1.33]; I2 = 0%; P < .001; NNT = 6), phenobarbital group (RR, 1.24 [95% CI, 1.13-1.35]; I2 = 12%; P < .001; NNT = 6), and ketamine group (RR, 1.39 [95% CI, 1.20-1.60]; I2 = 20%; P < .001; NNT = 5). There was no significant difference in the success rate of sedation between the rectal CH group and the midazolam group (RR, 0.98 [95% CI, 0.86-1.11]; I2 = 51%; P > .05). The sedation latency was significantly shorter in rectal CH group than that in the oral CH group (mean difference [MD], -6.36 [95% CI, -7.04 to -5.68]; I2 = 49%; P < .001) and the phenobarbital group (MD, -7.64 [95% CI, -9.12 to -6.16]; P < .00001). The sedation duration in the rectal CH group was significantly longer than in the oral CH group (MD, 6.43 [95% CI, 4.39-8.47]; I2 = 0%; P < .001). The overall incidence of adverse events was significantly lower with rectal CH than with oral CH (RR, 0.21 [95% CI, 0.16-0.29]; I2 = 45%; P < .001) and ketamine (RR, 0.26 [95% CI, 0.12-0.60]; I2 = 0%; P = .001). There was no significant difference in the overall incidence of adverse events with rectal CH compared with intramuscular midazolam (RR, 0.55 [95% CI, 0.23-1.28]; P = .17) and intranasal midazolam (RR, 3.00 [95% CI, 0.66-13.69]; P = .16). CONCLUSION: The available evidence suggests that rectal CH cloud be an effective and safe sedative agent for pediatric procedural sedation.

An in situ bioadhesive foam as a large intestinal delivery platform for antibody fragment to treat inflammatory bowel disease.

Biologics have been widely used as injectables in the treatment of inflammatory bowel disease (IBD). Different local treatment attempts have been developed in recent years. However, maintaining systemic levels of biologics is still crucial for achieving colitis remission. An equilibrium between systemic and local concentrations of biologics is therefore essential for treatment of colitis. Current formulations struggle to create optimal balance between drug concentrations in plasma and the colonic wall. Addressing this challenge, we developed a rectally delivered in situ foam that generates CO2via a reaction between potassium bicarbonate (PB) and citric acid (CA) without the aid of an external device. An anti-TNF-α antibody fragment (Fab) was loaded into the foam formulation, which promoted prolonged colon retention and improved Fab distribution up to proximal colon following rectal administration to mice. In addition, we observed increased plasma Fab concentrations in mice receiving the rectal Fab foam compared to a Fab solution. In a non-everted rat gut ex vivo model, a single exposure to the CO2-containing foam improved macromolecule transepithelial flux across colonic tissue by over ten-fold. Foam efficacy for Fab was investigated in a range of colitis mouse models, from acute to chronic. This non-invasive formulation platform demonstrates potential to overcome existing limitations in delivering biologics to inflamed colonic tissue.

Incidence of Post-ERCP Pancreatitis in Patients Receiving Rectal Indomethacin vs. Compounded Rectal Diclofenac Prophylaxis.

BACKGROUND AND AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) carries a 3-15% risk of post-ERCP pancreatitis (PEP). Rectal indomethacin reduces the risk of PEP, but its cost has increased more than 20-fold over the past decade. Rectal diclofenac is also used to prevent PEP but is not commercially available in the United States. The aim of this study is to compare the incidence of PEP after administration of commercially available rectal indomethacin versus compounded rectal diclofenac and assess financial implications. METHODS: ERCP cases at our institution with administration of 100 mg rectal indomethacin or 100 mg compounded rectal diclofenac between May 2018 and January 2022 were retrospectively reviewed. The incidence and severity of PEP was compared between the indomethacin (n = 728) and diclofenac (n = 304) groups. Risk factors (young age, female sex, history of pancreatitis or PEP, sphincterotomy during procedure, pancreatic indication, trainee involvement) and protective factors (prior sphincterotomy, pancreatic duct stenting) for PEP were compared between groups. RESULTS: 60 patients (8.2%) in the rectal indomethacin group and 25 patients (8.2%) in the compounded rectal diclofenac group developed PEP, resulting in moderate or severe PEP in 9 (15.0%) and 2 (8.0%) patients, respectively. The compounded rectal diclofenac group had more trainee involvement (46.1% vs. 32.8%, p = 0.0001) and more prior sphincterotomy cases (15.8% vs. 10.6%, p = 0.0193) compared to the rectal indomethacin group; no statistically significant differences were observed in all other risk and protective factors. Following switch to compounded rectal diclofenac, institutional annual cost savings amounted to $441,460.62 and patient charge decreased 45-fold. CONCLUSION: This retrospective single-center real-world analysis showed similar efficacy of rectal indomethacin and compounded rectal diclofenac in preventing PEP but demonstrates substantial cost savings after switching to compounded rectal diclofenac.

A temperature-responsive dual-hormone foam nanoengine improves rectal absorptivity of insulin-pramlintide for diabetes treatment.

Despite the therapeutic benefits of insulin-pramlintide dual-hormone therapy in diabetes, its application potential has been limited due to a lack of efficient delivery routes. Here, we developed a temperature-responsive dual-hormone foam nanoengine (HormFoam) and combined it with a customized spraying device to further construct an in situ foam-generating system for improving the rectal bioavailability of dual-hormone therapy. To support rapid clinical translation, a continuous microfluidic preparation for HormFoam was proposed, including the power unit of perfluorocarbon nanodroplets and the pharmaceutical components Pluronic F127-functionalized liposomal insulin and pramlintide. We found that HormFoam could consistently generate foams to drive drugs forward after rectal administration, which enhanced intestinal distribution and mucosa absorption, leading to systemic codelivery of insulin-pramlintide. HormFoam reproduced the physiology of endocrine pancreas for glycemic control and induced body weight loss while reversing metabolic disorders in diabetic mice with good biosafety. Therefore, HormFoam represents a state-of-the-art dual-hormone regimen with the potential to address unmet needs in diabetes management.

Indomethacin Does Not Reduce Post-ERCP Pancreatitis in High-Risk Patients Receiving Pancreatic Stenting.

BACKGROUND: Rectal indomethacin reduces pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP). However, there is insufficient evidence regarding its added benefits in patients already receiving prophylactic pancreatic stenting. Our goal was to evaluate the impact of indomethacin in high-risk patients undergoing pancreatic stenting. METHODS: A cohort study was conducted on all patients who underwent the rescue cannulation technique for challenging bile duct cannulation (selected high-risk patients). Patients were split into two groups based on the prophylaxis method for post-ERCP pancreatitis (PEP): one receiving a combination of indomethacin and pancreatic stenting, while the other received pancreatic stenting alone. Comparative analyses were carried out on PEP, hyperamylasemia, gastrointestinal bleeding, and postoperative hospital stay among post-ERCP pancreatitis patients. RESULTS: Between November 2017 and May 2023, a total of 607 patients with native papillae were enrolled, with 140 grouped into the indomethacin plus stent group and 467 into the stent alone group. The overall PEP rate was 4.4% in the entire cohort, with no statistical differences observed between the groups in terms of PEP rates (P = 0.407), mild PEP (P = 0.340), moderate to severe PEP (P = 1.000), hyperamylasemia (P = 0.543), gastrointestinal bleeding (P = 0.392), and postoperative hospital stay (P = 0.521). Furthermore, sensitivity analysis using multivariable analysis also validated these findings. CONCLUSIONS: Indomethacin did not reduce the incidence or severity of PEP in high-risk patients who routinely received prophylactic pancreatic stent placement. Therefore, the additional administration of rectal indomethacin to further mitigate PEP appears to be not necessary.

Rectal versus vaginal progesterone administration for luteal phase support in the hormone replacement therapy frozen embryo transfer (HRT-FET) cycle: protocol for a non-inferiority randomised controlled trial.

INTRODUCTION: This study compares rectal administration with vaginal administration of progesterone as luteal phase support in hormone replacement therapy frozen embryo transfer (HRT-FET) cycles. The reason for comparing the two routes of administration is that rectal administration has been suggested to be more patient friendly. METHODS AND ANALYSIS: This study is a randomised controlled trial comparing the ongoing pregnancy rate (OPR) at week 12 in HRT-FET cycles after rectal administered progesterone as the only administered progesterone compared with a vaginal luteal phase support regimen. All patients are enrolled from a Danish public fertility clinic and randomised to one of two groups, with 305 patients receiving embryo transfer assigned to each group. Endometrial preparation includes 6 mg oestradiol daily. The intervention group receives rectally administered progesterone (400 mg/12 hours) and the control group receives vaginally administered progesterone (400 mg/12 hours). If P4 is <35 nmol/L on blastocyst transfer day an additional rectal luteal phase rescue regimen is started (control group). Thawing and transferring of a single autologous vitrified blastocyst is scheduled on the sixth day of progesterone administration in both groups. The power calculation is based on a non-inferiority analysis with an expected OPR in both groups of 44% and the upper limit of a one-sided 95% CI will exclude a difference in favour of the control group of more than 10.0%. An interim analysis will be conducted once half of the study population has been enrolled. ETHICS AND DISSEMINATION: The trial was approved on 21 November 2023 by the Danish National Ethical Committee and the Danish Medicines Agency and is authorised by the Clinical Trials Information System (EUCT number 2023-504616-15-02). All patients will provide informed consent before being enrolled in the study. The results will be published in an international journal. TRIAL REGISTRATION NUMBER: EUCT number: 2023-504616-15-02.

Thermo-activated in situ rectal gel preparation for Ibuprofen using eutectic mixture.

This study aimed to develop a thermosensitive in situ gel formulation for rectal delivery of Ibuprofen as an efficient alternative dosage form. Utilizing poloxamer 188, poloxamer 407, and HPMC via cold technique method, a thermosensitive in situ gel was successfully prepared. The concentration of Ibuprofen in the formulations was 1.2 % (w/w). The prepared gels underwent assessment for clarity, gelation temperature, gelation time, gel strength, spread ability, syringe-ability, pH, viscosity, FTIR, and drug content. The selected formulations exhibited a gelation temperature within the range of 30 °C to 36 °C, with consistent amount of drug soluble in the formulations (93 % - 110 %). Mucoadhesive studies, in vitro release tests, ex vivo modeling of drug release, kinetic studies modeling, and histopathology testing were also conducted. The formulation comprising 18 % poloxamer 407, 12 % poloxamer 188, and 1 % sodium chloride (FS15) demonstrated suitable gelation temperature and desirable drug release rate. In vitro drug release tests indicated completion within one hour for both FS10 (20 % P407 & 10 % P188) and FS15 (18 % P407 & 12 % P188), with consistent and predictable release patterns observed through kinetic modeling analysis. Microscopic histopathology examination confirmed the safety of the selected formula, exhibiting no irritation in the mucosal membrane of the sheep. In conclusion, Ibuprofen thermosensitive in situ gel presents a promising and convenient strategy as a rectal carrier and an alternative dosage form to solid suppositories.

Rectal versus intravenous administration of acetaminophen; Clinical investigation of plasma level, analgesic, and antipyretic effects on 6-month to 6-year-old children in Zabol city, Iran.

OBJECTIVES: Acetaminophen is the most widely antipyretic analgesic medicine used in adults and children worldwide. Rectal acetaminophen is widely used in children who resist or cannot take oral medications. This study was designed to compare the efficacy of rectal and IV acetaminophen in children with fever and mild to moderate pain. PATIENTS AND METHODS: Total 60 children aged six months to 6 years, with fever and pain, that were treated with rectal or intravenous acetaminophen were selected and assigned in two groups. The IV group received 10mg/kg paracetamol as an IV infusion, and the rectal group received a 15mg/kg dose immediately after admission. Pain score was calculated using the FLACC method, and the axillary temperature was recorded at baseline and then 0.5, 1, 2, 4, and 6hours after drug administration. Blood samples were collected at baseline and then at 30min-intervals for the first 90minutes. RESULTS: The trend of changes in mean pain score at different time intervals was significantly different between the two groups. Body temperature decrease was more prominent in the IV group. The plasma concentration increased in both groups significantly with time. This increase was sharper in the IV group, just in the first 60minutes after drug administration. CONCLUSIONS: IV acetaminophen has more rapid onset of action, while rectal dosage form control fever and pain for longer duration. Considering its favorable effects with ease of administration and lower cost, rectal acetaminophen can be a reasonable option in selected patients with pain or fever.

Effectiveness and tolerability of rectal ointment and suppositories containing sucralfate for hemorrhoidal symptoms: a prospective, 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.

Effect of hydrogel drug delivery system for treating ulcerative colitis: A preclinical meta-analysis.

Hydrogel drug delivery systems (DDSs) for treating ulcerative colitis (UC) have garnered attention. However, there is a lack of meta-analysis summarizing their effectiveness. Therefore, this study aimed to conduct a meta-analysis of pre-clinical evidence comparing hydrogel DDSs with free drug administration. Subgroup analyses were performed based on hydrogel materials (polysaccharide versus non-polysaccharide) and administration routes of the hydrogel DDSs (rectal versus oral). The outcome indicators included colon length, histological scores, tumor necrosis factor-α (TNF-α), zonula occludens protein 1(ZO-1), and area under the curve (AUC). The results confirmed the therapeutic enhancement of the hydrogel DDSs for UC compared with the free drug group. Notably, no significant differences were found between polysaccharide and non-polysaccharide materials, however, oral administration was found superior regarding TNF-α and AUC. In conclusion, oral hydrogel DDSs can serve as potential excellent dosage forms in oral colon -targeting DDSs, and in the design of colon hydrogel delivery systems, polysaccharides do not show advantages compared with other materials.

History of Rectal Product Use and Country of Residence Influence Preference for Rectal Microbicide Dosage Forms Among Young Sexual and Gender Minorities: A Multi-country Trial Comparing Placebo Douche, Suppository, and Insert Products.

The DESIRE Study (MTN-035) explored product preference among three placebo rectal microbicide (RM) formulations, a rectal douche (RD), a suppository, and an insert, among 210 sexually active transgender people and men who have sex with men in five counties: the United States, Peru, Thailand, South Africa, and Malawi. Participants used each product prior to receptive anal sex (RAS) for 1 month, following a randomly assigned sequence, then selected their preferred product via computer assisted self-interview. In-depth interviews examined reasons for preference. We compared product preference and prior product use by country to explore whether geographic location and experience with the similar products impacted preference. A majority in the United States (56%) and Peru (58%) and nearly half in South Africa (48%) preferred the douche. Most in Malawi (59%) preferred the suppository, while half in Thailand (50%) and nearly half in South Africa (47%) preferred the insert. Participants who preferred the douche described it as quick and easy, already routinized, and serving a dual purpose of cleansing and protecting. Those who preferred the insert found it small, portable, discreet, with quick dissolution. Those who preferred the suppository found the size and shape acceptable and liked the added lubrication it provided. Experience with product use varied by country. Participants with RD experience were significantly more likely to prefer the douche (p = 0.03). Diversifying availability of multiple RM dosage forms can increase uptake and improve HIV prevention efforts globally.

RESUMEN: El estudio DESIRE (MTN-035) exploró la preferencia de producto entre tres formulaciones de microbicida rectal (MR) de placebo, una ducha rectal, un supositorio y un inserto, entre 210 personas transgénero y hombres que tienen sexo con hombres en cinco países: los Estados Unidos, Perú., Tailandia, Sudáfrica y Malawi. Los participantes utilizaron cada producto antes del sexo anal receptive (SAR) durante un mes, siguiendo una secuencia asignada al azar, luego seleccionaron su producto preferido mediante una autoentrevista asistida por computadora. Las entrevistas en profundidad examinaron los motivos de preferencia. Comparamos la preferencia de producto y el uso previo del producto por país para explorar si la ubicación geográfica y la experiencia con la forma farmacéutica impactaron la preferencia. Una mayoría en los Estados Unidos (56%) y Perú (58%) y casi la mitad en Sudáfrica (48%) prefirieron la ducha rectal. La mayoría en Malawi (59%) prefirió el supositorio, mientras que la mitad en Tailandia (50%) y casi la mitad en Sudáfrica (47%) prefirió el inserto. Los participantes que prefirieron la ducha rectal la describieron como rápida y fácil, ya parte de su rutina y que tenía el doble propósito de limpiar y proteger. Los que prefirieron el inserto lo consideraron pequeño, portátil, discreto y de rápida disolución. Los que prefirieron el supositorio encontraron que tenía un tamaño y forma aceptables y proveía lubricación adicional. La experiencia con el uso del producto varió según el país. Los participantes con experiencia con duchas rectales tenían significativamente más probabilidades de preferir la ducha rectal (p = 0,03). Diversificar la disponibilidad de múltiples formas farmacéuticas de MR puede aumentar la aceptación y mejorar los esfuerzos de prevención del VIH a nivel mundial.

MMX mesalamine in ulcerative colitis: Major advantages towards classical mesalamine formulations.

Medical therapy is the cornerstone of ulcerative colitis (UC) management and aims to induce and maintain remission. In case of mild-to-moderate UC, mesalamine (5-ASA) is the first-line option. 5-ASA requires local release at the level of the inflamed mucosa to exert its therapeutic action. While rectal preparations are useful in distal colitis, in cases of UC of at least rectosigmoid extent, guidelines suggest the association of oral and rectal 5-ASA. Mesalamine with Multi Matrix System® technology (MMX mesalamine) is an oral, high-strength (1.2 g/tablet), once-daily formulation of 5-ASA, designed to provide delayed and prolonged release throughout the entire colon. Clinical trials demonstrated a strong efficacy in inducing and maintaining clinical and endoscopic remission in active mild-to-moderate UC. The efficacy is related to specific colonic drug-delivery, to its high-dosage and once-daily administration, thus improving patients' adherence and outcomes. The specific colonic-delivery is also associated with very low rates of systemic absorption and adverse events (AEs). With this comprehensive review we aimed to summarize current knowledge on MMX mesalamine in mild-to-moderate UC, in terms of clinical pharmacology, efficacy and safety, also compared to other 5-ASA products. In addition we provided an expert opinion on the topic, examining the implications on clinical practice.

A Phase 1 Clinical Trial to Assess the Safety and Pharmacokinetics of a Tenofovir Alafenamide/Elvitegravir Insert Administered Rectally for HIV Prevention.

BACKGROUND: On-demand topical products could be an important tool for human immunodeficiency virus (HIV) prevention. We evaluated the safety, pharmacokinetics, and ex vivo pharmacodynamics of a tenofovir alafenamide/elvitegravir (TAF/EVG, 20 mg/16 mg) insert administered rectally. METHODS: MTN-039 was a phase 1, open-label, single-arm, 2-dose study. Blood, rectal fluid, and rectal tissue were collected over 72 hours following rectal administration of 1 and 2 TAF/EVG inserts for each participant. RESULTS: TAF/EVG inserts were safe and well tolerated. EVG and tenofovir (TFV) were detected in blood plasma at low concentrations: median peak concentrations after 2 inserts were EVG 2.4 ng/mL and TFV 4.4 ng/mL. Rectal tissue EVG peaked at 2 hours (median, 2 inserts = 9 ng/mg) but declined to below limit of quantification in the majority of samples at 24 hours, whereas tenofovir diphosphate (TFV-DP) remained high >2000 fmol/million cells for 72 hours with 2 inserts. Compared to baseline, median cumulative log10 HIV p24 antigen of ex vivo rectal tissue HIV infection was reduced at each time point for both 1 and 2 inserts (P < .065 and P < .039, respectively). DISCUSSION: Rectal administration of TAF/EVG inserts achieved high rectal tissue concentrations of EVG and TFV-DP with low systemic drug exposure and demonstrable ex vivo inhibition of HIV infection for 72 hours. Clinical Trials Registration . NCT04047420.

Penciclovir pharmacokinetics after oral and rectal administration of famciclovir in African elephants (Loxodonta africana) shows that effective concentrations can be achieved from rectal administration, despite lower absorption.

OBJECTIVE: To evaluate the pharmacokinetics of famciclovir and its metabolite penciclovir following a single dose administered orally and rectally in African elephants (Loxodonta africana). ANIMALS: 15 African elephants (6 males and 9 females) of various ages. METHODS: Famciclovir (15 mg/kg) was administered orally or per rectum once, with at least a three-week washout period between administrations. Blood was collected at 13 different timepoints per administration for 6 elephants, occurring between February and March 2020. An additional 9 elephants were sampled at variable timepoints per administration utilizing a sparse sampling design between July 2020 and January 2021. Plasma famciclovir and penciclovir levels were measured via HPLC and fluorescence detection. Pharmacokinetic analysis was completed in the summer of 2021 using noncompartmental analysis and nonlinear mixed-effects modeling. RESULTS: Famciclovir was not detected in any sample, suggesting complete metabolism. Key pharmacokinetic parameters for penciclovir following oral administration were time to maximum concentration (tmax; 2.12 hours), area under the concentration-versus-time curve (AUC; 33.93 µg·h/mL), maximum observed concentration (Cmax; 3.73 µg/mL), and absorption half-life (t1/2; 0.65 hours). Following rectal administration, the values were: tmax, 0.65 hours; AUC, 15.62 µg·h/mL; Cmax, 2.52 µg/mL; and absorption t1/2, 0.13 hours. CONCLUSIONS: Famciclovir was rapidly metabolized to penciclovir. Oral administration resulted in slower absorption but higher maximum plasma concentration and higher AUC compared to rectal administration. CLINICAL RELEVANCE: African elephants administered famciclovir via oral and rectal routes resulted in measurable serum penciclovir, and these findings may be utilized by clinicians treating viral infections in this species.

Lipid-Gelucire based rectal delivery of ramipril prodrug exhibits significant lowering of intra-ocular pressure in normotensive rabbit: sustained structural relaxation release kinetics and IVIVC.

Carboxylesterase enzymes convert a prodrug ramipril into the biologically active metabolite ramiprilat. It is prescribed for controlling ocular hypertension after oral administration. High concentrations of carboxylesterase enzymes in rectal and colon tissue can transform ramipril significantly to ramiprilat. Sustained rectal delivery of ramipril has been developed for intra-ocular pressure lowering effect using a normotensive rabbit model. Rectal suppositories have been formulated using a matrix base of HPMC K100-PEG 400-PEG 6000, incorporating varying amounts of Gelucire by the fusion moulding method. The presence of Gelucire in the suppository exhibited sustained structural relaxation-based release kinetics of RM compared to its absence. Intravenous and oral administration of ramipril has decreased IOP in the treated rabbit up to 90 and 360 min, respectively. Treated rabbits with suppositories have revealed decreased IOP for an extended period compared to the above. Formulation containing GEL 3% reduced intra-ocular pressure to 540 min, with the highest area under the decreased IOP curve. Compared to oral, the pharmacodynamic bioavailability of ramipril has been improved significantly using a sustained-release rectal suppository. A rectal suppository for sustained delivery of ramipril could be used to lower IOP significantly.

Non-Invasive Delivery of Insulin for Breaching Hindrances against Diabetes.

Insulin is recognized as a crucial weapon in managing diabetes. Subcutaneous (s.c.) injections are the traditional approach for insulin administration, which usually have many limitations. Numerous alternative (non-invasive) slants through different routes have been explored by the researchers for making needle-free delivery of insulin for attaining its augmented absorption as well as bioavailability. The current review delineating numerous pros and cons of several novel approaches of non-invasive insulin delivery by overcoming many of their hurdles. Primary information on the topic was gathered by searching scholarly articles from PubMed added with extraction of data from auxiliary manuscripts. Many approaches (discussed in the article) are meant for the delivery of a safe, effective, stable, and patient friendly administration of insulin via buccal, oral, inhalational, transdermal, intranasal, ocular, vaginal and rectal routes. Few of them have proven their clinical efficacy for maintaining the glycemic levels, whereas others are under the investigational pipe line. The developed products are comprising of many advanced micro/nano composite technologies and few of them might be entering into the market in near future, thereby garnishing the hopes of millions of diabetics who are under the network of s.c. insulin injections.