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Clinical Drug Investigation Jul 2023PSD502 is a metered-dose spray for premature ejaculation. The two trials aimed to evaluate the safety and pharmacokinetics of PSD502 in healthy Chinese male and female... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND OBJECTIVE
PSD502 is a metered-dose spray for premature ejaculation. The two trials aimed to evaluate the safety and pharmacokinetics of PSD502 in healthy Chinese male and female individuals.
METHODS
Two phase I, randomized, double-blind, placebo-controlled trials were conducted in men (Trial 1) and women (Trial 2). The participants were randomized 3:1 to receive PSD502 (7.5 mg of lidocaine and 2.5 mg of prilocaine per spray) or a placebo. For male individuals, a single dose (three sprays) once daily was applied to the glans penis for 21 days except for nine sprays (three doses) on days 7 and 14, 4 h apart for each dose. For female individuals, two sprays were applied to the vagina and one to the cervix once daily for 7 days. The primary endpoint was safety. Pharmacokinetics analysis was also performed.
RESULTS
Twenty-four male and 24 female individuals were recruited. Treatment-emergent adverse events occurred in 38.9% (7/18) of male individuals and 66.7% (12/18) of female individuals in the PSD502 group, respectively. Both trials reported 50.0% (3/6) treatment-emergent adverse events for the placebo. No grade ≥ 3 treatment-emergent adverse events, serious adverse events, or treatment-emergent adverse events leading to early withdrawal or discontinuation occurred. After consecutive applications, lidocaine and prilocaine cleared rapidly in both trials. Plasma concentrations exhibited high inter-individual variability. The maximum plasma concentrations of active ingredients were far below the anticipated minimum toxic concentrations. The area under the plasma concentration-time curve of metabolites were ≤ 20% of the parent drugs. No clinically significant accumulations were observed in the two trials.
CONCLUSIONS
PSD502 was well tolerated and showed low plasma concentrations in healthy Chinese male and female individuals.
Topics: Female; Humans; Male; Double-Blind Method; East Asian People; Healthy Volunteers; Lidocaine; Lidocaine, Prilocaine Drug Combination; Prilocaine; Premature Ejaculation; Administration, Topical; Penis; Vagina; Cervix Uteri
PubMed: 37380910
DOI: 10.1007/s40261-023-01277-4 -
Anaesthesia, Critical Care & Pain... Dec 2023Spinal anesthesia with intrathecal morphine (ITM) is a common anesthesia technique for cesarean delivery. The hypothesis was that the addition of ITM will delay... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Spinal anesthesia with intrathecal morphine (ITM) is a common anesthesia technique for cesarean delivery. The hypothesis was that the addition of ITM will delay micturition in women undergoing cesarean delivery.
METHODS
Fifty-six ASA physical status I and II women scheduled to undergo elective cesarean delivery under spinal anesthesia were randomized to the PSM group (50 mg prilocaine + 2.5 mcg sufentanil + 100 mcg morphine; n = 30) or PS group (50 mg prilocaine + 2.5 mcg sufentanil; n = 24). The patients in the PS group received a bilateral transverse abdominal plane (TAP) block. The primary outcome was the effect of ITM on the time to micturition and the secondary outcome was the need for bladder re-catheterization.
RESULTS
The time to first urge to urinate (8 [6-10] hours in the PSM group versus 6 [4-6] hours in the PS group) and the time to first micturition (10 [8-12] hours in the PSM group versus 6 [6-8] hours in the PS group) were significantly (p < 0.001) prolonged in the PSM group. Two patients in the PSM group met the 800 mL criterium for urinary catheterization after 6 and 8 h respectively.
CONCLUSION
This study is the first randomized trial to demonstrate that the addition of ITM to the standardized mixture of prilocaine and sufentanil significantly delayed micturition.
Topics: Pregnancy; Humans; Female; Morphine; Sufentanil; Urinary Bladder; Analgesics, Opioid; Pain, Postoperative; Prilocaine; Double-Blind Method
PubMed: 37364852
DOI: 10.1016/j.accpm.2023.101269 -
BMC Pediatrics Jun 2023To characterize clinical profile of pediatric local anesthetic (LA) systemic toxicity (LAST) and to identify determinants of life-threatening outcomes.
PURPOSE
To characterize clinical profile of pediatric local anesthetic (LA) systemic toxicity (LAST) and to identify determinants of life-threatening outcomes.
METHODS
Spontaneous reports notified to the French Pharmacovigilance Network were retrieved and followed by a case-by-case review, according to the following criteria: LA as suspected drug, age < 18 years, adverse drug reactions related to nervous system, cardiac, respiratory, psychiatric or general disorders. Multivariate logistic regression analysis was performed to identify factors leading to life-threatening reaction (i.e. continuous seizures or cardiorespiratory arrest).
RESULTS
Among 512 cases retrieved, 64 LAST cases were included (neonates 11%, infants 30%, children 36%, adolescents 23%) mainly involving lidocaine (47%), lidocaine + prilocaine (22%) and ropivacaine (14%). Toxicity profiles were neurological (58%), cardiac (11%) or mixed (20%) and 7 patients (11%) developed methemoglobinemia. LAST was life-threatening for 23 patients (36%) and 2 patients died. Doses were above recommendations in 26 patients (41%) and were not different between life-threatening and non-life-threatening cases. The context of use (general and orthopedic surgery, p = 0.006) and the type of LA agent (lidocaine, p = 0.016) were independently associated with a life-threatening outcome.
CONCLUSION
In this national retrospective analysis, LAST in children appear to be a rare event. Neurological and cardiac signs were the most frequently reported reactions. LAST in children can be life-threatening, even at therapeutic doses. Although a fatal outcome may anecdotally occur, the vast majority of patients recovered after appropriate medical care.
Topics: Infant; Infant, Newborn; Adolescent; Humans; Child; Anesthetics, Local; Pharmacovigilance; Retrospective Studies; Lidocaine; Ropivacaine; Lidocaine, Prilocaine Drug Combination
PubMed: 37355586
DOI: 10.1186/s12887-023-04126-7 -
Frontiers in Bioengineering and... 2023Liver cancer is now one of the main causes leading to death worldwide. To achieve reliable therapeutic effects, it is crucial to develop efficient approaches to test...
Liver cancer is now one of the main causes leading to death worldwide. To achieve reliable therapeutic effects, it is crucial to develop efficient approaches to test novel anticancer drugs. Considering the significant contribution of tumor microenvironment to cell's response to medications, 3D bioinspiration of cancer cell niches can be regarded as an advanced strategy to improve the accuracy and reliability of the drug-based treatment. In this regard, decellularized plant tissues can perform as suitable 3D scaffolds for mammalian cell culture to create a near-to-real condition to test drug efficacy. Here, we developed a novel 3D natural scaffold made from decellularized tomato hairy leaves (hereafter called as DTL) to mimic the microenvironment of human hepatocellular carcinoma (HCC) for pharmaceutical purposes. The surface hydrophilicity, mechanical properties, and topography measurement and molecular analyses revealed that the 3D DTL scaffold is an ideal candidate for liver cancer modeling. The cells exhibited a higher growth and proliferation rate within the DTL scaffold, as verified by quantifying the expression of related genes, DAPI staining, and SEM imaging of the cells. Moreover, prilocaine, an anticancer drug, showed a higher effectiveness against the cancer cells cultured on the 3D DTL scaffold, compared to a 2D platform. Taken together, this new cellulosic 3D scaffold can be confidently proposed for chemotherapeutic testing of drugs on hepatocellular carcinoma.
PubMed: 37251569
DOI: 10.3389/fbioe.2023.1189726 -
Current Pharmaceutical Design May 2023Local anesthetic (LA) compounds decrease the permeability of the ion channels to sodium, which in turn, diminishes the rate of depolarization. These agents (a.k.a....
Local anesthetic (LA) compounds decrease the permeability of the ion channels to sodium, which in turn, diminishes the rate of depolarization. These agents (a.k.a. -caines) are also used to depress mucosal sensations, e.g., gag reflex in the form of topical anesthetics. Overdose of LA can lead to local anesthetic systemic toxicity (LAST), which is the precursor of potentially lethal consequences on clinical grounds. There is a wide array of possible presentations of LAST, from mild findings, such as temporary hypertensive events, to serious conditions, including refractory cardiac dysfunction, dysrhythmias and prearrest situations. Lidocaine, prilocaine, mepivacaine, ropivacaine, and bupivacaine are among the most commonly used members of the family. The agents' dosages should be adjusted in children, elderly and fragile individuals and those with organ failures, as the metabolism of the compounds will be impaired. The ideal body weight, along with hepatic and renal functional reserves, will have an impact on elimination kinetics. Systemic absorption is an untoward consequence of LA administration which deserves every means of prevention. Intravenous lipid emulsion is an important life-saving treatment in severe, life-threatening cases. This narrative review article is designed to cover the clinical uses of LA in children, recognition, and management of untoward effects of the agents, with special emphasis on the LAST.
PubMed: 37231720
DOI: 10.2174/1381612829666230525122040 -
The Journal of Craniofacial Surgery Oct 2023The most common typical symptoms of keloids can be pain and itchiness. Intralesional corticosteroid administration is generally the first-line conservative treatment....
BACKGROUND
The most common typical symptoms of keloids can be pain and itchiness. Intralesional corticosteroid administration is generally the first-line conservative treatment. Minimizing pain during intralesional corticosteroid injections into keloids should be aimed, as the treatment is often painful. There has yet to be a report on which local anesthetic technique is superior in keloid treatment between topical anesthetic versus lidocaine mixture injection.
METHODS
This was a single-center prospective study. The study included 100 patients with painful multiple/multifocal keloids aged 18 to 85 years and was performed between May 2021 and December 2022. Among multiple keloid lesions in a single patient, we assigned the keloids pretreated with topical cream application versus local injection. Then, subjects received 40 mg of intralesional corticosteroid injections into the keloids with a 26G needle to treat keloids. Patients rated the pain intensity of each lesion pretreated with two different anesthetic techniques on an 11-point numeric rating scale. A separate direct question of "Which technique would you recommend if you had to be injected again?" was given.
RESULTS
One-hundred patients with painful multiple/multifocal keloids were included in the study. Data on pain intensity numeric rating scale (NRS) revealed that injection techniques relieved the pain statistically significantly more than topical creams. ( P <0.001) 63% of the participants (n=63) preferred the injection technique, while 25% preferred topical anesthetics. In total, 12% of patients responded that there was no difference between the two techniques.
CONCLUSION
When comparing with topical lidocaine/prilocaine (EMLA) cream, a 1:1 mixture of 1% lidocaine and epinephrine significantly alleviated pain during and after the corticosteroid injection.
Topics: Humans; Adrenal Cortex Hormones; Anesthetics, Local; Injections, Intralesional; Keloid; Lidocaine; Pain; Prilocaine; Prospective Studies; Male; Female; Adolescent; Adult; Middle Aged; Aged; Aged, 80 and over
PubMed: 37220648
DOI: 10.1097/SCS.0000000000009438 -
Dental Research Journal 2023This study aimed to compare the success rate of inferior alveolar nerve (IAN) anesthesia in the mandibular first molars with symptomatic irreversible pulpitis using two...
Comparison of the success of inferior alveolar nerve anesthesia in the mandibular first molars with symptomatic irreversible pulpitis using two anesthetic solutions of prilocaine and mepivacaine: A randomized controlled clinical trial.
BACKGROUND
This study aimed to compare the success rate of inferior alveolar nerve (IAN) anesthesia in the mandibular first molars with symptomatic irreversible pulpitis using two anesthetic solutions of prilocaine and mepivacaine.
MATERIALS AND METHODS
The current randomized controlled clinical trial was conducted on 100 patients in two groups ( = 50). Standard injection of IAN block (IANB) was performed using two cartridges of 3% mepivacaine plain in the first group and using two cartridges of 3% prilocaine with 0.03 IU felypressin in the second group. Fifteen minutes after injection, the patients were asked about lip anesthesia. In case of a positive answer, the tooth was isolated with a rubber dam. Success was defined as no or mild pain on the basis of the visual analog scale recording upon access cavity preparation, entry into the pulp chamber, and initial instrumentation. Data were analyzed with SPSS 17 using the Chi-square test, and < 0.05 was set as statistically significant.
RESULTS
The patients' pain severities during the three stages were significantly different ( = 0.001, 0.0001, and 0.001, respectively). The success rate of IANB during access cavity preparation was 88% with prilocaine and 68% with mepivacaine. This rate during entry into the pulp chamber was 78% and 24%, respectively, which was 3.25 times higher with prilocaine than mepivacaine. The success rates during instrumentation were 32% and 10%, respectively, which was 3.2 times higher with prilocaine than mepivacaine.
CONCLUSION
The success rate of IANB in the teeth with symptomatic irreversible pulpitis was higher using 3% prilocaine with felypressin than using 3% mepivacaine.
PubMed: 37180689
DOI: No ID Found -
CJEM Jun 2023The objective of this study was to synthesize indication-based evidence for NO for distress and pain in children. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The objective of this study was to synthesize indication-based evidence for NO for distress and pain in children.
STUDY DESIGN
We included trials of NO in participants 0-21 years, reporting distress or pain for emergency department procedures. The primary outcome was procedural distress. Where meta-analysis was not possible, we used Tricco et al.'s classification of "neutral" (p ≥ 0.05), "favorable," or "unfavorable" (p < 0.05, supporting NO or comparator, respectively). We used the Cochrane Collaboration's Risk of Bias tool and the Grading of Recommendations Assessment, Development, and Evaluation system to evaluate risk of bias and quality of evidence, respectively.
RESULTS
We included 30 trials. For pain using the Visual Analog Scale (0-100 mm) during IV insertion, 70% NO (delta:-16.5; 95%CI:-28.6 to -4.4; p = 0.008; three trials; I = 0%) and 50% NO plus eutectic mixture of local anesthetics (EMLA) (delta:-1.2; 95%CI:-2.1 to -0.3; p = 0.007; two trials; I = 43%) were superior to EMLA. 50% NO was not superior to EMLA (delta:-0.4; 95%CI:-1.2 to 0.3; p = 0.26; two trials; I = 15%). For distress and pain during laceration repair, NO was "favorable" versus each of SC lidocaine, oxygen, and oral midazolam but "neutral" versus IV ketamine (five trials). For distress and pain during fracture reduction (three trials), NO was "neutral" versus each of IM meperidine plus promethazine, regional anesthesia, and IV ketamine plus midazolam. For distress and pain during lumbar puncture (one trial), NO was "favorable" versus oxygen. For distress and pain during urethral catheterization (one trial), NO was "neutral" versus oral midazolam. For pain during intramuscular injection (one trial), NO plus EMLA was "favorable" versus NO and EMLA alone. Common adverse effects of NO included nausea (4.4%), agitation (3.7%), and vomiting (3.6%) AEs were less frequent with NO alone (278/1147 (24.2%)) versus NO plus midazolam (48/52 (92.3%)) and NO plus fentanyl (123/201 (61.2%)).
CONCLUSIONS
There is sufficient evidence to recommend NO plus topical anesthetic for IV insertion and laceration repair. Adverse effects are greater when combined with other sedating agents.
Topics: Child; Adolescent; Humans; Nitrous Oxide; Midazolam; Ketamine; Lacerations; Pain; Anesthetics, Local; Lidocaine, Prilocaine Drug Combination; Oxygen
PubMed: 37171705
DOI: 10.1007/s43678-023-00507-0 -
Pediatric Emergency Care Mar 2024Several pain management tools exist but with limitations in their efficacy or applicability. The EMLA (eutectic mixture of local anesthetics) cream is currently used for... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
Several pain management tools exist but with limitations in their efficacy or applicability. The EMLA (eutectic mixture of local anesthetics) cream is currently used for pain relief for needle-related procedures; however, it needs a minimum of 30 to 45 minutes to be effective. The Buzzy is a device that generates vibrations with cold leading to quicker pain relief. Our aim was to evaluate the effect of the Buzzy device in pain and anxiety reduction compared with EMLA cream in children requiring intravenous cannulation or venepuncture.
METHODS
This was a randomized clinical trial comparing pain and anxiety reduction by Buzzy device with the standard care (EMLA cream) in children aged 2 to 14 years who required blood extraction or intravenous cannulation based on their clinical needs. Eligible patients were randomized to either Buzzy device as the intervention or EMLA cream as the control. The outcome measures were the degree of pain scores and anxiety ratings at different stages of the needle-related procedures.
RESULTS
A total of 300 patients with a mean age of 6.5 ± 3.1 years were enrolled. Baseline characteristics were similar between the Buzzy device and EMLA cream groups. The observed pain scores by research nurses and a parent were significantly lower in the EMLA group compared with the Buzzy device group; however, the pain scores by the self-assessment scale were not statistically significant with mean difference of -0.332, 95% confidence interval, -0.635 to -0.028 ( P = 0.062). The level of anxiety was significantly lower in EMLA compared with Buzzy device ( P = 0. 0.0001). Both staff and parents' satisfaction, success rate of cannulation, type of blood tests, and comment on the physician on the results were similar in both groups.
CONCLUSIONS
Pain and anxiety relief using the Buzzy device is not as effective as EMLA cream in children requiring venepuncture. However, rapid onset of action of the Buzzy device is valuable in decreasing waiting time in a busy emergency department.
TRIAL REGISTRATION
clinicaltrials.gov Identifier: NCT05354739.
Topics: Child; Humans; Child, Preschool; Lidocaine, Prilocaine Drug Combination; Lidocaine; Pain; Anesthetics, Local; Phlebotomy; Prilocaine
PubMed: 37163686
DOI: 10.1097/PEC.0000000000002965