Clinical Pharmacology : Advances and Applications最新文献

{"title":"Antiviral Combination Clinically Better Than Standard Therapy in Severe but Not in Non-Severe COVID-19.","authors":"Prasan Kumar Panda,&nbsp;Budha O Singh,&nbsp;Bikram Moirangthem,&nbsp;Yogesh Arvind Bahurupi,&nbsp;Sarama Saha,&nbsp;Girraj Saini,&nbsp;Minakshi Dhar,&nbsp;Mukesh Bairwa,&nbsp;Venkatesh Srinivasa Pai,&nbsp;Ankit Agarwal,&nbsp;Girish Sindhwani,&nbsp;Shailendra Handu,&nbsp;Ravi Kant","doi":"10.2147/CPAA.S325083","DOIUrl":"https://doi.org/10.2147/CPAA.S325083","url":null,"abstract":"<p><strong>Purpose: </strong>Definitive antiviral treatment is not available for COVID-19 infection, with the exception of remdesivir, which still evokes many doubts. Various monotherapy or combination therapies with antivirals or other agents have been tried. The present study aims to evaluate the therapeutic potential of hydroxychloroquine and lopinavir-ritonavir in combination with ribavirin in mild-severe COVID-19.</p><p><strong>Patients and methods: </strong>A single-center, open-label, parallel-arm, stratified randomized controlled trial evaluated the therapeutic potential of combination antiviral therapies. Enrolled patients in the severe category were randomized into three groups: (A) standard treatment, (B) hydroxychloroquine+ribavirin+standard treatment, or (C) lopinavir+ritonavir+ribavirin+standard treatment; while the non-severe category comprised two groups: (A) standard treatment or (B) hydroxychloroquine+ribavirin. Combination antivirals were given for 10 days and followed for 28 days. The primary endpoints were safety, symptomatic and laboratory recovery of organ dysfunctions, and time to SARS-CoV-2 RT-PCR negative report.</p><p><strong>Results: </strong>In total, 111 patients were randomized: 24, 23, and 24 in severe categories A, B, and C, respectively, and 20 in each of the non-severe groups. Two patients receiving ribavirin experienced drug induced liver injury, and another developed QT prolongation after hydroxychloroquine. In the severe category, 47.6%, 55%, and 30.09% in A, B, and C groups, respectively, showed symptomatic recovery, compared to 93.3% and 86.7% in A and B groups, respectively, in the non-severe category at 72 hours (<i>P</i>>0.05).</p><p><strong>Conclusion: </strong>Though the results failed to show statistical superiority of the antiviral combination therapies to that of the standard therapy in both the severe and non-severe categories in symptomatic adult patients of COVID-19 due to very small sized trial, clinically hydroxychloroquine+ribavirin therapy is showing better recovery by 7.4% than standard therapy in the former category. However, results do indicate the benefit of standard therapy in the non-severe category by 6.6%. Furthermore, the dose of ribavirin needs to be reconsidered in the Indian population.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":" ","pages":"185-195"},"PeriodicalIF":2.0,"publicationDate":"2021-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a9/26/cpaa-13-185.PMC8487855.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39491460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-Xa Inhibitor-Induced Hemorrhagic Pruritic Rash: A Case Report on Possible Cross-Reactivity Between Apixaban and Rivaroxaban.","authors":"Takla R Anis,&nbsp;Whitney Jandreau","doi":"10.2147/CPAA.S325430","DOIUrl":"https://doi.org/10.2147/CPAA.S325430","url":null,"abstract":"<p><p>Direct oral anticoagulants (DOACs) have gained increasing popularity in clinical practice in the past decade. While DOACs have fewer associated adverse events as compared to warfarin, DOAC-induced hypersensitivity is a rare adverse event that has been reported in the literature. We describe a case of apixaban-induced hemorrhagic pruritic rash in a 62-year-old man with protein C deficiency for which he was receiving warfarin. During hospitalization for another issue, his anticoagulant was converted to apixaban. Within 6 hours of receiving the first dose of apixaban, he developed a hemorrhagic pruritic rash around his buttocks area and extending into his groin. The following day, apixaban was replaced with rivaroxaban, while the rash continued to worsen and spread further around his back. After 3 days of DOAC therapy, the patient was reverted back to warfarin and within 24 hours the rash subsided. This case report indicates a potential rare adverse drug reaction that may become more prominent given the increasing utilization of DOACs in clinical practice. Future research is needed to further investigate this adverse event and ensure that providers and patients are aware of it. Additionally, this report documents to our knowledge, the first report of an immediate hypersensitivity reaction to DOACs.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":" ","pages":"181-184"},"PeriodicalIF":2.0,"publicationDate":"2021-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f0/cd/cpaa-13-181.PMC8487854.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39491459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the Pharmacokinetics of Trazpiroben (TAK-906), a Peripherally Selective D₂/D₃ Dopamine Receptor Antagonist, in the Presence and Absence of Itraconazole, a Potent CYP 3A4 Inhibitor.","authors":"Chunlin Chen,&nbsp;Wenwen Zhang,&nbsp;Muhammad Bari,&nbsp;Cristina Almansa,&nbsp;Mike Baratta,&nbsp;Maria Rosario","doi":"10.2147/CPAA.S310609","DOIUrl":"https://doi.org/10.2147/CPAA.S310609","url":null,"abstract":"<p><strong>Purpose: </strong>Treatment options for gastroparesis, such as metoclopramide and domperidone, are limited because of safety concerns, which may be exacerbated in the presence of inhibitors of drug metabolism. This study evaluated the effect of itraconazole on the pharmacokinetics, safety, and tolerability of trazpiroben (previously TAK-906), a novel, peripherally selective D₂/D₃ dopamine receptor antagonist.</p><p><strong>Methods: </strong>This was a phase 1, two-period, crossover trial in healthy participants (NCT03161405). On day 1, period 1 (days 1-3), participants received a single oral dose of trazpiroben 25 mg. During period 2 (days 4-9), participants received oral itraconazole 200 mg once daily (days 1-5) and one oral dose of trazpiroben 25 mg post itraconazole on day 4. Trazpiroben pharmacokinetics were assessed. Safety assessments included triplicate electrocardiograms.</p><p><strong>Results: </strong>Twelve healthy males (24-45 years old) were studied. Co-administration of itraconazole increased trazpiroben area under the concentration-time curve from time 0 to infinity by 1.28-fold (90% confidence interval: 1.10, 1.49) and maximum plasma concentration (C_max) by 1.98-fold (1.64, 2.39) versus trazpiroben alone. Placebo-corrected, change from baseline in corrected QT interval at the observed geometric mean C_max for trazpiroben alone (9.53 ng/mL) and with itraconazole (18.00 ng/mL) was estimated at 1.31 ms (-0.39, 3.01) and 1.54 ms (-0.15, 3.24), respectively. There were no clinically relevant abnormalities in any safety parameters.</p><p><strong>Conclusion: </strong>These results indicate that TAK‑906 is relatively insensitive to inhibition of cytochrome P450 3A4, and cardiovascular safety concerns associated with domperidone are unlikely to be elicited by trazpiroben under similar conditions.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":" ","pages":"145-155"},"PeriodicalIF":2.0,"publicationDate":"2021-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a9/53/cpaa-13-145.PMC8285519.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39206710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Guselkumab for the Treatment of Palmoplantar Pustulosis: A Japanese Perspective.","authors":"Toshiyuki Yamamoto","doi":"10.2147/CPAA.S266223","DOIUrl":"https://doi.org/10.2147/CPAA.S266223","url":null,"abstract":"<p><p>Palmoplantar pustulosis (PPP) is a chronic inflammatory disorder characterized by sterile pustules predominantly involving the palms and soles. PPP is refractory to various therapies such as topical ointment, oral medicine, and phototherapies. Pustulotic arthro-osteitis (PAO) is a major comorbidity of PPP that severely impairs patients' quality of life. Recently, guselkumab, a monoclonal antibody against IL-23, has been available for the treatment of PPP in Japan. The purpose of the present review is to describe the characteristics of Japanese PPP patients and biologic therapy of PPP/PAO using guselkumab. Most Japanese dermatologists consider PPP as a distinct entity and co-existence of PPP and psoriasis is rare. However, outside Japan, PPP is often considered to be palmoplantar psoriasis, and extra-palmoplantar lesions associated with PPP are regarded as psoriasis. PPP develops or exacerbates either with or without arthralgia, following focal infections, such as tonsillitis, odontogenic infection, and sinusitis. Treatment of focal infection results in dramatic effects on cutaneous lesions as well as joint pain. By contrast, we sometimes see patients whose skin/joint symptoms do not improve after treatment of focal infection, whose focus of infection cannot be identified even in a detailed examination, and/or who refuse tonsillectomy even if strongly recommended. Such cases are considered to be indications of biologics. In this review, clinical features, pathophysiology and guselkumab therapy are discussed.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":" ","pages":"135-143"},"PeriodicalIF":2.0,"publicationDate":"2021-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d4/08/cpaa-13-135.PMC8236264.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39121716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the MK2 Inhibitor ATI-450 in Healthy Subjects: A Placebo-Controlled, Randomized Phase 1 Study.","authors":"David Gordon,&nbsp;Edward T Hellriegel,&nbsp;Heidi Rath Hope,&nbsp;David Burt,&nbsp;Joseph B Monahan","doi":"10.2147/CPAA.S305308","DOIUrl":"https://doi.org/10.2147/CPAA.S305308","url":null,"abstract":"<p><strong>Purpose: </strong>ATI-450 is an oral, small-molecule inhibitor of the p38α mitogen-activated protein kinase (MAPK)/MAPK-activated protein kinase 2 (MK2) inflammatory signaling pathway. This phase 1, single and multiple ascending dose (SAD, MAD) study evaluated ATI-450 safety, tolerability, pharmacokinetics, and pharmacodynamics.</p><p><strong>Patients and methods: </strong>Healthy adults were randomly assigned to SAD (10, 30, 50, 100 mg; n=24) and MAD (10, 30, 50 mg twice daily [BID] for 7 days; n=24) cohorts of ATI-450 or placebo (n=14). Safety and tolerability were evaluated through clinical and laboratory assessments. Pharmacokinetic parameters were evaluated in plasma samples; pharmacodynamic assessments included quantification of cytokine levels (tumor necrosis factor α [TNF-α], interleukin [IL]-1β, IL-6, IL-8) and phosphorylation of the MK2 downstream substrate, heat shock protein 27 (p-HSP27).</p><p><strong>Results: </strong>The most common adverse events were headache (10/48, 20.8%), dizziness (6/48, 12.5%), upper respiratory tract infection (3/48, 6.3%), and constipation (3/48, 6.3%). Pharmacokinetics were dose-proportional, with a terminal half-life of 9‒12 hours in the MAD cohorts on day 7. Dose- and concentration-dependent inhibition of ex vivo stimulated cytokines and target biomarker was observed. On day 7, patients in the 50 mg BID dose cohort recorded mean trough drug levels that were 1.4, 2.2, 2.3, and 2.4 times greater than the IC₈₀ for TNF-α, IL-1β, IL-8, and p-HSP27, respectively. Mean C_max was 3.5, 5.4, 5.6, and 6.0 times greater than the IC₈₀ for TNF-α, IL-1β, IL-8, and p-HSP27, respectively. IL-6 inhibition >50% was noted for part of the dosing interval.</p><p><strong>Conclusion: </strong>ATI-450 was well tolerated at the doses investigated, exhibited dose- and time-independent (ie, linear) pharmacokinetics, and dose-related pharmacodynamic effects. These results support further study of ATI-450 in immunoinflammatory diseases in phase 2 trials.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":" ","pages":"123-134"},"PeriodicalIF":2.0,"publicationDate":"2021-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/49/e4/cpaa-13-123.PMC8203602.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39243751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rupatadine Oral Solution Titration by Body Weight in Paediatric Patients Suffering from Allergic Rhinitis: A Population Pharmacokinetic Study.","authors":"Eva Santamaria,&nbsp;Iñaki Izquierdo,&nbsp;Marta Valle","doi":"10.2147/CPAA.S312911","DOIUrl":"https://doi.org/10.2147/CPAA.S312911","url":null,"abstract":"<p><strong>Background: </strong>Allergic rhinitis (AR) and chronic urticaria, both are treated in children with doses of second generation of antihistamines that have been mostly based on extrapolation of data obtained in adults. The objectives of this work were to develop a model to explain the pharmacokinetics (PK) of rupatadine, a second generation antihistamine, administered to children 2-11 years old and to calculate the non-compartmental PK parameters for two groups of age (2-5 and 6-11 years old) based on the individual Bayesian estimates from the selected model.</p><p><strong>Methods: </strong>Data from two PK studies with rupatadine oral solution (1 mg/mL) were pooled: Study A, an extensive blood sampling study performed in 11 children (6-11 years old) who received a single oral dose of rupatadine; and Study B, a sparse blood sampling study in 40 children (2-5 years old) receiving multiple oral doses. A simultaneous population PK model was developed using data available for all children. Using individual Bayesian estimates from the selected model, steady-state plasma concentrations for both studies were simulated and the non-parametric PK parameters were calculated for two age groups: 2-5 years (subgroup I) and 6-11 years (subgroup II).</p><p><strong>Results: </strong>A two-compartment model with first-order absorption and elimination with clearance depending on body weight, better described the PK of rupatadine for 2-11 year old children. The plasma clearance dependence on weight was linear. The mean (SD) non-compartment PK parameters calculated using simulated plasma profiles at steady state were: C_max, 2.54 (1.26) vs 1.96 (0.52) ng/mL; AUC_0-24h, 10.74 (3.09) vs 10.38 (4.31) ng/mL/h; and t_1/2, 12.28 (3.09) vs 15.94 (4.09) h, for children 6-11 and 2-5 years old, respectively.</p><p><strong>Conclusions: </strong>The PK of rupatadine depends on the weight of paediatric patients but not on their age. The dosage strategy adjusted by body weight in children 2-11 years old (2.5 mL if weight 10-25 kg, and 5 mL if ≥ 25 kg) provides similar exposure between the two groups of age, and to that obtained in adults with the 10 mg dose tablet formulation.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":" ","pages":"115-122"},"PeriodicalIF":2.0,"publicationDate":"2021-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a1/fc/cpaa-13-115.PMC8197573.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39237593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Determination of Caffeine and Hydrogen Peroxide Antioxidant Activity of Raw and Roasted Coffee Beans Around Habru Woreda, Ethiopia Using UV-Vis Spectroscopy.","authors":"Beshir Legas Muhammed,&nbsp;Mohammed Hussen Seid,&nbsp;Adere Tarekegne Habte","doi":"10.2147/CPAA.S311032","DOIUrl":"https://doi.org/10.2147/CPAA.S311032","url":null,"abstract":"<p><strong>Background: </strong>Coffee is a well-known beverage that is widely used around the world. Despite the wide use of coffee in Ethiopia, there is a lack of extensive studies addressing the issues related to the caffeine content and hydrogen peroxide antioxidant activity of varieties of coffee types, particularly in Habru woreda, Ethiopia.</p><p><strong>Objective: </strong>This study aimed to determine the caffeine content and hydrogen peroxide antioxidant activity of raw and roasted coffee beans collected directly from Habru woreda, North Wollo zone of Ethiopia.</p><p><strong>Methods: </strong>The study was conducted in Bohoro, Girana, and Wurgisa kebeles of Habru woreda, Ethiopia, by collecting 500 g of green beans of Arabica coffee without considering their variety. Then, the collected beans were divided into raw and roasted coffee to perform aqueous and dichloromethane extraction of their caffeine content and hydrogen peroxide antioxidant activity using UV-Vis spectrophotometry.</p><p><strong>Results: </strong>The amounts of caffeine in aqueous and dichloromethane extraction were in the range of 124.01-191.27 ppm and 145.15-200.09 ppm in raw and roasted coffees, respectively. Using the IC₅₀ value, the hydrogen peroxide scavenging activity of the aqueous phase coffee bean extracts in Bohoro raw, Bohoro roasted, Wurgisa raw, Wurgisa roasted, Girana raw, and Girana roasted coffee were 32.17 ppm, 11.69 ppm, 26.14 ppm, 3.12 ppm, 24.83 ppm, and 11.06 ppm, respectively, while that of ascorbic acid was 6.91 ppm.</p><p><strong>Conclusion: </strong>The study showed that the highest amount of caffeine in both aqueous and dichloromethane solvent extraction was found in Bohoro's raw and roasted coffee beans. Also, the amounts of caffeine in all coffee bean samples were safe and the antioxidant activity was excellent. In most of the samples, significant variations in the concentration of caffeine in raw and roasted coffee bean samples were observed in the two extraction solvents.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":" ","pages":"101-113"},"PeriodicalIF":2.0,"publicationDate":"2021-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5b/cc/cpaa-13-101.PMC8163633.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39055535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial Assessing Efficacy and Safety of a Novel Low-Dose Turmeric Extract Formulation in Healthy Adults with Chronic Knee Pain.","authors":"Shefali Thanawala, Rajat Shah, Venkateswarlu Somepalli, KrishnaRaju Venkata Alluri, Prabakaran Desomayanandam, Arun Bhuvanendran","doi":"10.2147/CPAA.S307464","DOIUrl":"10.2147/CPAA.S307464","url":null,"abstract":"<p><strong>Background: </strong>Knee pain causes functional limitations, eventually compromising the quality of life. We evaluated the efficacy of our water-dispersible turmeric formulation (60% natural curcuminoids, TurmXTRA 60N^®-WDTE60N), which exhibited better PK profile at low dose (250 mg) than standard turmeric extract, in alleviating symptoms of chronic knee pain.</p><p><strong>Methods: </strong>In this randomized, double-blind, placebo-controlled trial, subjects received either 250 mg WDTE60N capsule (150 mg curcuminoids; n = 53) or appearance-matched placebo capsule (n = 53) once daily for 90 days. Primary endpoint was change in pain score on the visual analogue scale (VAS) after 80-m fast-paced walk test.</p><p><strong>Results: </strong>A total of 96 subjects completed the study. WDTE60N reduced VAS score from baseline (5.4 ± 0.9) to day 90 (3.8 ± 0.8) with greater mean reduction than placebo (-1.5 ± 0.7 vs -0.6 ± 0.8, <i>p</i> < 0.0001; 2.5 times). It also significantly improved the time taken for 80-m fast-paced walk test and 9-step stair-climb test; and improved all biomarkers compared to placebo (<i>p</i> > 0.05). Three adverse events occurred but were unrelated to study products.</p><p><strong>Conclusion: </strong>WDTE60N 250 mg administered once daily for 3 months, alleviated knee pain, improved joint function in healthy subjects with chronic knee pain, was well tolerated and safe.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"13 ","pages":"91-100"},"PeriodicalIF":3.1,"publicationDate":"2021-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/95/ad/cpaa-13-91.PMC8149286.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9727011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Investigator-Initiated, Prospective, Single-Center, Open-Label Clinical Study to Evaluate Safety and Performance of Intra-Articular Hyaluronic Acid (IA-HA) (Biovisc Ortho) in Patients with Osteoarthritis (OA) of the Knee.","authors":"Ajay Gupta,&nbsp;Chethan Channaveera,&nbsp;Vijender Anand,&nbsp;Satyaranjan Sethi","doi":"10.2147/CPAA.S298589","DOIUrl":"https://doi.org/10.2147/CPAA.S298589","url":null,"abstract":"<p><strong>Objective: </strong>IA-HA is injected into the osteoarthritis knee as a viscosupplementation for therapeutic purposes. This clinical trial was carried out for evaluating the efficacy and safety of Biovisc Ortho IA-HA (20 mg/2 mL) in a 2 mL prefilled syringe.</p><p><strong>Design: </strong>The study was conducted as an open-label, single-center, single-arm clinical trial in India. Patients of knee OA with moderate to severe symptoms for a minimum duration of 3 months were included in the study. Five visits were conducted at weekly intervals and the investigational product was administered at each visit. Two follow-up visits were conducted at 3 and 6 months after the completion of the last injection cycle. The primary outcome variable was change in KOOS pain score from baseline. The secondary outcome variables were analyzed for other KOOS scales and safety of the device.</p><p><strong>Results: </strong>Change in KOOS pain score at 6 months from baseline was 29.71±15.74 and the change in mean KOOS score for pain was statistically significant (<i>p</i><0.0001) for all post-baseline visits. Statistically significant improvement was observed for mean values of efficacy assessments (KOOS) during the study period (6 months) for all the domains evaluated, including pain, joint function and quality of life.</p><p><strong>Conclusion: </strong>Despite being an open, noncomparative study, the safety and efficacy results of IA-HA establish the therapeutic effect of the treatment throughout the study period of 6 months and are safe.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":" ","pages":"73-82"},"PeriodicalIF":2.0,"publicationDate":"2021-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0a/13/cpaa-13-73.PMC8123980.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38996516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metformin as a Potential Adjuvant Antimicrobial Agent Against Multidrug Resistant Bacteria.","authors":"Majed M Masadeh,&nbsp;Karem H Alzoubi,&nbsp;Majd M Masadeh,&nbsp;Zainah O Aburashed","doi":"10.2147/CPAA.S297903","DOIUrl":"https://doi.org/10.2147/CPAA.S297903","url":null,"abstract":"<p><strong>Introduction: </strong>The continuous increase in the incidence of bacterial resistance to existing antibiotics represents a worldwide health burden. A surrogate strategy to combat such crisis is to find compounds that restore the antimicrobial activity of the already existing antibiotics against multidrug resistant bacteria. Metformin is a commonly used antidiabetic medication. It has proven benefits in other diseases including cancer, aging-related and infectious diseases. In this study, the potential effect of metformin as an adjuvant therapy to antibiotics was investigated.</p><p><strong>Methods: </strong>Two multidrug resistant bacterial strains were used; methicillin-resistant <i>Staphylococcus aureus</i> (MRSA; ATCC 33,591) and multidrug resistant <i>Pseudomonas aeruginosa</i> (ATCC BAA-2114). To assess its efficacy, metformin was combined with several antibiotics: levofloxacin, chloramphenicol, rifampicin, ampicillin, and doxycycline. The antibacterial effect of metformin was tested using the micro broth dilution method. The minimum inhibitory concentration (MIC) was also measured. Cytotoxicity studies were also performed on mammalian cells to assess its safety.</p><p><strong>Results: </strong>Metformin exhibited an antibacterial effect when combined with the antibiotics on the two tested strains. It also showed low toxicity on the mammalian cells. Moreover, synergetic studies showed that metformin enhanced the effect of the combined antibiotics, as these combinations provide either a synergistic or additive effect with significant reduction in the MIC.</p><p><strong>Conclusion: </strong>Metformin exerts an adjuvant antibacterial effect; thus, it could be a possible candidate as an adjuvant therapy to reduce antimicrobial resistance.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":" ","pages":"83-90"},"PeriodicalIF":2.0,"publicationDate":"2021-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/54/10/cpaa-13-83.PMC8123943.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38996517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}