BACKGROUND: GB-5001 is an intramuscular (IM) formulation of donepezil under development for the treatment of Alzheimer\'s disease. The objective of this study was to develop a population pharmacokinetic (PK) model for donepezil in both IM and oral formulations, and to optimize the IM dosage of GB-5001 using bioequivalence (BE) simulation.
METHODS: A population PK model of donepezil was developed using NONMEM. It was based on plasma concentration data from a Phase 1 dose escalation study, which involved a single administration of donepezil IM formulation at doses of 70, 140, and 280 mg, and the oral formulation at 10 mg. The model was evaluated based on goodness-of-fit plots, conditional weighted residuals, visual predictive checks, and bootstrapping. BE simulations were conducted using a parallel design between various doses of the IM formulation and the 10-mg dose of oral formulation.
RESULTS: The PKs of donepezil were best described by a two-compartment model, which incorporated distinct absorption compartments for the IM (dual first-order absorption and simultaneous zero-order absorption with lag time) and oral (first-order absorption with lag time) formulations. Based on the simulation results, an IM dosage range of 210-215 mg in a sample size of over 92 was estimated to achieve a success rate of approximately 80% for BE.
CONCLUSIONS: The population PK model well explained the PKs of donepezil following administration of both the IM and oral formulations. This model could be applied for the design and dose selection of future BE trials.
BACKGROUND: ClinicalTrials.gov identifier, NCT05525780.

UNASSIGNED: Intramuscular (IM) injections deliver a plethora of drugs. The majority of IM-related literature details dissolution and/or pharmacokinetic (PK) studies, using methods with limited assessments of post-injection events that can impact drug fate, and absorption parameters. Food and Drug Association guidelines no longer require preclinical in vivo modeling in the U.S.A. Preclinical animal models fail to correlate with clinical outcomes, highlighting the need to study, and understand, IM drug fate in vitro using bespoke models emulating human IM sites. Post-IM injection events, i.e. underlying processes that influence PK outcomes, remain unacknowledged, complicating the application of in vitro methods in preclinical drug development. Understanding such events could guide approaches to predict and modulate IM drug fate in humans.
UNASSIGNED: This article reviews challenges in biorelevant IM site modeling (i.e. modeling drug fate outcomes), the value of technologies available for developing IM injectables, methods for studying drug fate, and technologies for training in performing IM administrations. PubMed, Web-of-Science, and Lens databases provided papers published between 2014 and 2024.
UNASSIGNED: IM drug research is expanding what injectable therapeutics can achieve. However, post-injection events that influence PK outcomes remain poorly understood. Until addressed, advances in IM drug development will not realize their full potential.

BACKGROUND: Benzodiazepines are the recommended first-line treatment of acute seizures. We wished to compare the efficacy, side effects, and satisfaction after midazolam administration by the buccal, intranasal, or intramuscular route in the treatment of acute seizures in children at homes and in emergency room (ER).
METHODS: A prospective, randomized, controlled trial was performed in children aged one month to 17 years with acute seizures lasting longer than five minutes. The primary end point was seizure cessation within 10 minutes of drug administration and no seizure recurrence within 30 minutes.
RESULTS: In the home group, 67 patients received midazolam via buccal route, 60 via intranasal route, and 69 via intramuscular route, whereas in the ER group, 37 patients received buccal, 34 received intranasal, and 34 received intramuscular midazolam. The primary end point was achieved in 94.2% and 85.3% after intramuscular midazolam in the home and ER groups, respectively. The intranasal midazolam was successful in stopping seizures in 93.3% in the home group and 88.2% in the ER group. The buccal route was effective in 91% in the home group and 78.4% in the ER group. There were no significant differences in efficacy between all groups (P = 0.763 and P = 0.509) among the home and ER groups, respectively. There were no significant cardiorespiratory events in all groups.
CONCLUSIONS: Intramuscular, intranasal, and buccal doses of midazolam resolved most seizures in prehospital and emergency settings. Our results indicate that there is no statistically significant difference detected between different routes of midazolam. Intranasal route showed the highest satisfaction rate among caregivers.

UNASSIGNED: Long-acting injectable (LAI) antipsychotic medications can help improve treatment adherence in patients with schizophrenia and bipolar disorder. Despite this, they are underutilized. In 2003, intramuscular risperidone became the first available LAI atypical antipsychotic medication, and since then, a number of competing long-acting risperidone formulations have been brought to market, with additional options under active development. These include intramuscular, subcutaneous, long-acting oral, and implantable formulations.
UNASSIGNED: This review summarizes currently available and emerging long-acting risperidone formulations, including efficacy and safety data, and practical considerations aimed to help prescribers distinguish one formulation from another.
UNASSIGNED: There is an expanding number of currently available LAI antipsychotic medications giving patients and providers an opportunity to personalize and individualize care. Rates of adherence to treatment in patients with schizophrenia and bipolar disorder are low, and individualizing care can help improve this. The risperidone LAI treatment landscape includes five options approved by the U.S. Food and Drug Administration, with others under clinical development. These options differ in regard to mode of administration, approved indications, available dose strengths, injection intervals, needle size, injection volume, storage, and other variables. Prescribers should be familiar with these differing options to help patients find the best fit for their individual needs.

UNASSIGNED: Botulinum toxin has played a remarkable role in management of forehead wrinkles. Most used is intramuscular technique due to its deposition into the muscles, however, with adverse effects like brow ptosis. This study has been designed for the evaluation of efficacy for intradermal v/s intramuscular route of botulinum toxin injections for forehead wrinkles using clinical correlation.
UNASSIGNED: This study included a clinical trial of 32 facial halves divided equally into intradermal and intramuscular injection technique groups, receiving total dose of 8 U. Results were assessed by clinical examination upto 2 weeks and 4 weeks with parameters; objective wrinkle rate, eyebrow height, eyebrow movement, pain, and satisfaction after treatment.
UNASSIGNED: Results showed least mean for objective wrinkle rate in intramuscular group, showing statistically significant improvement. Overall improvement in eyebrow height and eyebrow movement were slightly more for intramuscular group. Pain was lesser for intradermal group, whereas satisfaction of patient of patient post treatment is similar for both the groups.
UNASSIGNED: Among intradermal and intramuscular botulinum toxin injection technique, the effect and potency were better for intramuscular technique, whereas the patient comfort and compliance were better for intradermal technique.

BACKGROUND: A BCG booster vaccination administered via the respiratory mucosa may establish protective immune responses at the primary site of Mycobacterium tuberculosis infection. The primary objective of this trial was to compare the safety and immunogenicity of inhaled versus intramuscular administered ChAdOx1-85A.
METHODS: We conducted a single-centre, randomised, double-blind, controlled phase 1 study (Swiss National Clinical Trials Portal number SNCTP000002920). After a dose-escalation vaccination in nine BCG-vaccinated healthy adults, a dose of 1 × 1010 vp of ChAdOx1-85A was administered to twenty BCG-vaccinated adults that were randomly allocated (1:1) into two groups: aerosol ChAdOx1-85A with intramuscular saline placebo or intramuscular ChAdOx1-85A with aerosol saline placebo, using block randomisation. A control group of ten BCG-naïve adults received aerosol ChAdOx1-85A at the same dose. Primary outcomes were solicited and unsolicited adverse events (AEs) up to day 16 post-vaccination and Serious AEs (SAEs) up to 24 weeks; secondary outcomes were cell-mediated and humoral immune responses in blood and bronchoalveolar lavage (BAL) samples.
RESULTS: Both vaccination routes were well tolerated with no SAEs. Intramuscular ChAdOx1-85A was associated with more local AEs (mostly pain at the injection site) than aerosol ChAdOx1-85A. Systemic AEs occurred in all groups, mainly fatigue and headaches, without differences between groups. Respiratory AEs were not different between BCG-vaccinated groups. Aerosol ChAdOx1-85A vaccination induced Ag85A BAL and systemic cellular immune responses with compartmentalisation of the immune responses: aerosol ChAdOx1-85A induced stronger BAL cellular responses, particularly IFNγ/IL17+CD4+ T cells; intramuscular ChAdOx1-85A induced stronger systemic cellular and humoral responses.
CONCLUSIONS: Inhaled ChAdOx1-85A was well-tolerated and induced lung mucosal and systemic Ag85A-specific T-cell responses. These data support further evaluation of aerosol ChAdOx1-85A and other viral vectors as a BCG-booster vaccination strategy.

Intramuscular lipomas, typically found in subcutaneous tissue, rarely affect deeper muscular planes, especially those of the head and neck region. The following are 3 cases of intramuscular lipomas involving the sternocleidomastoid muscle. The first 2 patients presented with painless, palpable masses confirmed by diagnostic imaging as well-circumscribed intramuscular lipomas. One was treated surgically, while the other was managed conservatively with monitoring and close follow-up. The third patient reported dysphagia associated with occasional dyspnea and mild pain. The mass was identified as infiltrative lipoma and was resected surgically. Complete tumor removal with no recurrence at 6 months was observed for the first and last cases. The second case was serially followed at 3 and 6 months with no interval changes. We report the largest case series on intramuscular lipomas of the sternocleidomastoid muscle to enhance our understanding of this rare entity.

OBJECTIVE: Compartment syndrome remains difficult to diagnose early in its clinical course. Pressure transducer catheters have been used to directly measure intracompartmental pressure (ICP), but this method is unreliable, with a false positive rate of 35%. We have previously used intramuscular near infrared spectroscopy to detect changes in tissue oxygen saturation (StO2) in response to increasing ICP using a novel implantable probe. However, measuring StO2 may not be sufficient to identify CS in the clinical setting. The pathophysiology of CS consists of increased ICP, leading to decreased tissue perfusion, and resulting in reduced tissue oxygenation. More clinically useful information may come from the integration of multiple data streams to aid in the diagnosis of CS. In this study, we present a novel, intramuscular probe capable of simultaneous measurement of ICP, StO2, and microvascular blood flow in a porcine model of ACS.
METHODS: Proof of concept for this device is demonstrated in a porcine lower extremity balloon compression model of ACS. Pressure was maintained for 20 min (short-term) or 3 h (long-term) before the balloon volume was removed.
RESULTS: In both short- and long-term experiments, as ICP increased with increasing balloon volume, the novel multimodal sensor simultaneously and reliably detected pressure elevation and corresponding reversible reductions in microvascular flow rate and tissue oxygenation.
CONCLUSIONS: This novel trimodal device simultaneously measured the elevated ICP, decreased perfusion, and tissue ischemia of evolving ACS, substantiating our basic understanding of CS pathophysiology.

UNASSIGNED: Ganglion cysts in the thigh area are uncommon, typically occurring in the wrist and ankle. These cysts are usually painless but may compress nearby structures, causing discomfort. Ultrasound is a valuable tool to differentiate ganglion cysts from hematomas and lipomas. It also helps identify the fluid-filled cyst walls. Treatment typically involves surgical removal, with complete resection being the goal.
METHODS: We present a case of a woman who experienced a gradual increase in size of a lump in her groin area. The lump was later diagnosed and completely removed. Histological analysis revealed the presence of a ganglion cyst.
UNASSIGNED: Clinical examination is crucial for diagnosing superficial ganglion cysts. It allows us to assess their separation from the skin and connection to deeper structures. It\'s important to consider ganglion cysts as part of the differential diagnosis for cystic lesions in the groin area during routine medical practice. This can help avoid unnecessary and expensive tests like MRI scans in some cases.
CONCLUSIONS: Developing a thorough differential diagnosis for uncommon lesions in specific anatomical areas is essential in clinical practice. This aids in choosing appropriate diagnostic methods and surgical intervention, if necessary, to prevent recurrence of the condition.

BACKGROUND: Rheumatic Heart Disease (RHD) persists as a major cardiovascular driver of mortality and morbidity among young people in low-and middle-income countries. Secondary antibiotic prophylaxis (SAP) with penicillin remains the cornerstone of RHD control, however, suboptimal treatment adherence undermines most secondary prevention programs. Many of the barriers to optimal SAP adherence are specific to the intramuscular form of penicillin and may potentially be overcome by use of oral penicillin. This noninferiority trial is comparing the efficacy of intramuscular to oral penicillin SAP to prevent progression of mild RHD at 2 years.
METHODS: The Intramuscular vs Enteral Penicillin Prophylaxis to Prevent Progression of Rheumatic Heart Disease (GOALIE) trial is randomizing Ugandan children aged 5 to 17 years identified by echocardiographic screening with mild RHD (Stage A or B as defined by 2023 World Heart Federation criteria) to Benzathine Benzyl Penicillin G (BPG arm, every-28-day intramuscular penicillin) or Phenoxymethyl Penicillin (Pen V arm, twice daily oral penicillin) for a period of 2 years. A blinded echocardiography adjudication panel of 3 RHD experts and 2 cardiologists is determining the echocardiographic stage of RHD at enrollment and will do the same at study completion by consensus review. Treatment adherence and study retention are supported through peer support groups and case management strategies. The primary outcome is the proportion of children in the Pen V arm who progress to more advanced RHD compared to those in the BPG arm. Secondary outcomes are patient-reported outcomes (treatment acceptance, satisfaction, and health related quality of life), costs, and cost-effectiveness of oral compared to intramuscular penicillin prophylaxis for RHD. A total sample size of 1,004 participants will provide 90% power to demonstrate noninferiority using a margin of 4% with allowance for 7% loss to follow-up. Participant enrollment commenced in October 2023 and final participant follow-up is expected in December 2026. The graphical abstract (Fig. 1) summarizes the flow of echocardiographic screening, participant enrollment and follow-up.
CONCLUSIONS: The GOALIE trial is critical in global efforts to refine a pragmatic approach to secondary prevention for RHD control. GOALIE insists that the inferiority of oral penicillin be proven contemporarily and against the most important near-term clinical outcome of progression of RHD severity. This work also considers other factors that could influence the adoption of oral prophylaxis and change the calculus for acceptable efficacy including patient-reported outcomes and costs.
BACKGROUND: ClinicalTrials.gov: NCT05693545.