Clinical Pharmacology : Advances and Applications最新文献

{"title":"Impact of Routine Platelet Reactivity Testing with VerifyNow Assay on Antiplatelet Choice After Percutaneous Coronary Intervention.","authors":"Fakilahyel S Mshelbwala,&nbsp;Daniel W Hugenberg,&nbsp;Rolf P Kreutz","doi":"10.2147/CPAA.S242675","DOIUrl":"https://doi.org/10.2147/CPAA.S242675","url":null,"abstract":"<p><strong>Background: </strong>High on-treatment ADP platelet reactivity (HPR) measured by VerifyNow P2Y12 assay (VN) is an established risk factor for ischemic events after percutaneous coronary intervention (PCI). We hypothesized that routine use of VN at time of PCI in clinical practice may affect choice of P2Y12 antiplatelet therapy at discharge.</p><p><strong>Methods: </strong>In a single center retrospective analysis, we examined the influence of VN testing on choice of P2Y12 inhibitor post PCI in routine clinical practice. Assessment of HPR was used routinely in clinical care during the time period of analysis at discretion of clinical providers. Subjects with PRU>208 after the loading dose of clopidogrel or during clopidogrel steady state were switched to alternate P2Y12 inhibitors.</p><p><strong>Results: </strong>We identified 1001 patients with PCI during the time period specified. A total of 252 subjects underwent VN testing. Among those, 43% were found to have HPR on clopidogrel and were switched to alternate therapies (prasugrel [n=60], ticagrelor [n=48]). Patients who had VN platelet function testing were more likely to be discharged on clopidogrel as compared to those who did not have VN assay done (57% vs. 50%, p=0.039). There was no significant difference in 1-year net-MACE (CVD, MI, stent thrombosis, BARC 2 or higher bleeding) using tailored antiplatelet therapy (VN testing) as compared to standard of care group (adjusted HR:0.92, 95% CI: 0.54-1.5, p=0.74).</p><p><strong>Conclusion: </strong>Routine use of VN assay in personalized antiplatelet treatment decision-making after PCI is associated with lower likelihood of using novel P2Y12 inhibitors.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"12 ","pages":"35-41"},"PeriodicalIF":2.0,"publicationDate":"2020-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S242675","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37901243","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":"Pharmacokinetics, Safety, and Preliminary Efficacy of Oral Trifluridine/Tipiracil in Chinese Patients with Solid Tumors: A Phase 1b, Open-Label Study.","authors":"Xicheng Wang,&nbsp;Jianfeng Zhou,&nbsp;Yan Li,&nbsp;Yuping Ge,&nbsp;Yanping Zhou,&nbsp;Chunmei Bai,&nbsp;Lin Shen","doi":"10.2147/CPAA.S232104","DOIUrl":"https://doi.org/10.2147/CPAA.S232104","url":null,"abstract":"<p><strong>Purpose: </strong>Trifluridine/tipiracil (FTD/TPI) is approved in Japan, the United States (US), and Europe for metastatic colorectal cancer (mCRC) refractory to standard therapies. This Phase 1b open-label study focused on the pharmacokinetic (PK) and toxicity profiles of FTD/TPI in Chinese patients with solid tumors.</p><p><strong>Methods: </strong>Patients with definitive histologically or cytologically confirmed advanced/metastatic solid tumors refractory to standard treatments were enrolled. FTD/TPI (35 mg/m²) was administered orally twice daily for five consecutive days, followed by a 2-day recovery. Treatment was repeated for five consecutive days, followed by a 16-day recovery. The primary objective was to assess PK characteristics of FTD, 5-trifluoromethyl-2,4 (1H,3H)-pyrimidinedione (FTY; an inactive form of FTD), and TPI, calculated from plasma concentrations. Additionally, these PK values were compared with those from similar Phase 1 studies in patients from Japan and the US, using Tukey-Kramer's honestly significant difference (HSD) multiple comparison tests. Safety and preliminary efficacy of FTD/TPI were assessed.</p><p><strong>Results: </strong>Fifteen patients (12 males, three females) were enrolled, most with CRC (87%). Geometric mean analysis showed that maximum plasma concentration (C_max) of FTD increased after multiple administration (from day 1 [3019.5 ng/mL] to day 12 [3693.1 ng/mL]), and the exposure (AUC_0-t) increased 2.4-fold (day 1:7796.6 ng/mL•h; day 12:18,181.3 ng/mL•h). There was no meaningful change in the exposure to FTY and TPI throughout the study. HSD tests showed comparable PK for FTD, FTY, and TPI between Chinese and Japanese patients, and comparable exposure to FTD between Chinese and US patients. Eight patients (53.3%) experienced Grade 3 treatment-emergent adverse events, most frequently anemia and fatigue (13.3%, two events each). Median progression-free survival was 1.9 months.</p><p><strong>Conclusion: </strong>FTD/TPI had an acceptable safety and efficacy profile and PK characteristics were comparable between Chinese, Japanese, and US patients, suggesting that this treatment may be suitable for Chinese patients with refractory mCRC.</p><p><strong>Trial registration: </strong>This trial was registered at clinicaltrials.gov as NCT02261532.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"12 ","pages":"21-33"},"PeriodicalIF":2.0,"publicationDate":"2020-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S232104","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37851545","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 the Permeation and Penetration of Flurbiprofen into Cadaveric Human Pharynx Tissue.","authors":"Rob Turner,&nbsp;Sean Robert Wevrett,&nbsp;Suzanne Edmunds,&nbsp;Marc B Brown,&nbsp;Robert Atkinson,&nbsp;Oluwajoba Adegoke,&nbsp;Anuradha Kulasekaran,&nbsp;Tim Shea","doi":"10.2147/CPAA.S234227","DOIUrl":"https://doi.org/10.2147/CPAA.S234227","url":null,"abstract":"<p><strong>Objective: </strong>Flurbiprofen 8.75 mg spray and lozenge have a rapid onset of action for sore throat relief, suggesting local action, although tissue penetration and the mechanism of local relief have not been determined. This investigation aimed to quantify the permeation and penetration of flurbiprofen, applied as local pharmaceutical forms, into full-thickness cadaveric human mucosal pharynx tissue, representing the clinical scenario as far as possible.</p><p><strong>Methods: </strong>A validated high-performance liquid chromatography method quantified the permeation and penetration of flurbiprofen (spray and lozenge formulations) into human cadaveric pharynx tissue using a micro Franz cell model mimicking physiological and anatomical conditions. Full-thickness mucosal pharynx tissue, consisting of oral epithelium, basement membrane, and lamina propria, was utilized to imitate the in vivo setting. Flurbiprofen was analyzed on the surface of the pharynx tissue, within the pharynx tissue and in receiver fluid, over 60 mins.</p><p><strong>Results: </strong>Flurbiprofen was detected in receiver fluid from 10 mins following spray application and was quantifiable from 20 mins. Flurbiprofen from lozenge was detected from 10 mins and was above the limit of quantitation in receiver fluid from 40 mins. Flurbiprofen recovered from the surface of the pharynx tissue was 24.45% and 8.48% of applied dose for spray and lozenge, respectively. Flurbiprofen recovered within pharynx tissue was 46.50% and 54.65% of applied dose for spray and lozenge, respectively. For flurbiprofen lozenge, recovery within pharynx tissue was 6-fold higher relative to recovery from the pharynx tissue surface.</p><p><strong>Conclusion: </strong>Flurbiprofen from spray and lozenge formulations penetrated human cadaveric pharynx tissue, indicating that flurbiprofen can reach all layers of the pharynx mucosal tissue, including the underlying lamina propria, which contains blood vessels and nerve fibers that contribute to pain during sore throat. This suggests that flurbiprofen may have a local mechanism of action for sore throat, although this has yet to be determined.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"12 ","pages":"13-20"},"PeriodicalIF":2.0,"publicationDate":"2020-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S234227","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37821452","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 Single- and Multiple-Dose Study to Evaluate the Pharmacokinetics of Fixed-Dose Grazoprevir/Elbasvir in Healthy Chinese Participants.","authors":"Haiyan Li,&nbsp;Zhenhua Yang,&nbsp;Shuang Zhang,&nbsp;Lin Xu,&nbsp;Yudong Wei,&nbsp;Jun Jiang,&nbsp;Luzelena Caro,&nbsp;Hwa-Ping Feng,&nbsp;Jacqueline B McCrea,&nbsp;Meng Li,&nbsp;Shuang Xie,&nbsp;Jiangdian Wang,&nbsp;Xu Min Zhao,&nbsp;Shengmei Mu","doi":"10.2147/CPAA.S224662","DOIUrl":"https://doi.org/10.2147/CPAA.S224662","url":null,"abstract":"<p><strong>Purpose: </strong>The burden of hepatitis C virus infection is particularly high in Asian countries, and new treatments are urgently needed. The purpose of this study was to characterize the pharmacokinetics (PK) and safety of the fixed-dose combination tablet of elbasvir/grazoprevir in healthy Chinese participants.</p><p><strong>Patient and methods: </strong>In this Phase I, single-site, open-label, 3-period study in healthy Chinese adults, participants received a single tablet of elbasvir 50 mg/grazoprevir 100 mg, followed by blood sampling for up to 96 hrs (http://www.chinadrugtrials.org.cn/ CTR20160034; Protocol PN071). Participants then received 1 tablet daily for 10 days, followed by a minimum 10-day washout, after which participants received a single dose of 2 tablets (elbasvir 100 mg/grazoprevir 200 mg). Elbasvir and grazoprevir PK were assessed following single and multiple doses. Safety and tolerability were also evaluated.</p><p><strong>Results: </strong>Twelve participants (50% male) were enrolled in and completed the study. Following single-dose oral administration of elbasvir 50 mg/grazoprevir 100 mg or elbasvir 100 mg/grazoprevir 200 mg, the median T_max was 3-4 hrs and elimination half-life was 18 hrs (elbasvir) and 30 hrs (grazoprevir). Multiple-dose administration resulted in AUC_0-24 accumulation ratios of 1.58 (elbasvir) and 2.35 (grazoprevir). Both elbasvir 50 mg/grazoprevir 100 mg and 100 mg/200 mg regimens were generally well tolerated.</p><p><strong>Conclusion: </strong>Single-dose administration of elbasvir 50 mg/grazoprevir 100 mg or 100 mg/200 mg and once-daily administration of elbasvir 50 mg/grazoprevir 100 mg for 10 days has been adequately characterized, with PK values within the expected range, and was generally well tolerated in healthy Chinese male and female participants.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"12 ","pages":"1-11"},"PeriodicalIF":2.0,"publicationDate":"2020-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S224662","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37682138","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":"Metabolism and Excretion of Intravenous, Radio-Labeled Amisulpride in Healthy, Adult Volunteers","authors":"G. Fox, A. Roffel, J. Hartstra, Linda A Bussian, S. van Marle","doi":"10.2147/CPAA.S234256","DOIUrl":"https://doi.org/10.2147/CPAA.S234256","url":null,"abstract":"Purpose Intravenous amisulpride, a dopamine D2/D3 antagonist, has recently been shown in trials to be an effective antiemetic at low doses. This study was conducted to investigate the metabolism and elimination of a single dose of intravenous 14C-labeled amisulpride in healthy, adult volunteers. Patients and methods Six healthy male volunteers aged 18–65 years were given a single 10 mg dose of 14C-labeled amisulpride containing not more than 1.8 MBq of radioactivity, infused over 4 mins. Concentrations of amisulpride and total radioactivity were measured in plasma, whole blood, urine and feces at various time points up to 168 hrs after dosing. Metabolites detected in plasma, urine and feces were characterized using liquid chromatography tandem mass spectrometry (LC-MS/MS) with in-line radiometric detection. Results The mean recovery of radioactivity in excreta was 96.4% (range 92.0–98.5%), of which 73.6% (range 70.6–79.2%) was recovered from urine and 22.8% (range 18.9–25.7%) from feces. Four metabolites of amisulpride were detected in urine, representing 15.0% of the excreted dose; three of these were also present in feces, representing 6.1% of the excreted dose. No metabolites were detected in plasma. Excretion was initially rapid, with about two-thirds of the drug-related material eliminated within 12 hrs, primarily in the urine. A second, slower phase of excretion was predominantly fecal and was essentially complete by 96 hrs after dosing. The terminal plasma elimination half-life of parent amisulpride was 3.7 hrs and that of total 14C-labeled drug material was 4.2 hrs. Conclusion Intravenous amisulpride undergoes limited metabolism and is excreted primarily via the renal route. Clinical trial registry number ClinicalTrials.gov NCT02881840.","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"11 1","pages":"161 - 169"},"PeriodicalIF":2.0,"publicationDate":"2019-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S234256","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41654808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perioperative Administration of Emend® (Aprepitant) at a Tertiary Care Children’s Hospital: A 12-Month Survey","authors":"A. Kanaparthi, Sarah Kukura, N. Slenkovich, F. Alghamdi, Shabana Shafy, Mohammed Hakim, J. Tobias","doi":"10.2147/CPAA.S221736","DOIUrl":"https://doi.org/10.2147/CPAA.S221736","url":null,"abstract":"Introduction Aprepitant (Emend®) is a novel antiemetic agent that works through antagonism of neurokinin-1 (NK-1) receptors. To date, there are limited data regarding its use to prevent postoperative nausea and vomiting (PONV) in children. We retrospectively reviewed our initial 12-months experience with aprepitant after it was made available for perioperative use. Methods The anesthetic records of patients who received aprepitant were retrospectively reviewed and demographic, surgical, and medication data retrieved. Results The study cohort included 31 patients (15 male and 16 female) ranging in age from 4 to 27 years (15.7 ± 7.4 years) and in weight from 14.4 to 175.7 kilograms (59.3 ± 30.2 kgs). Most of the patients (30 of 31) received the capsule form and 1 received the liquid. The average dose of aprepitant administered was 0.9 ± 0.6 mg/kg; however, only one patient received dosing expressed as mg/kg, and the majority received a 40 mg capsule. All of the patients in the cohort had either a previous history of PONV or risk factors for PONV. PONV occurred in the PACU in 1 patient and during the first 24 postoperative hours in 3 additional patients. No adverse effects related to aprepitant use were noted. Conclusion Aprepitant was easily added to the preoperative regimen for pediatric patients who may require it. Our approach limited overuse and subsequent cost concerns. Future studies with a comparator group and a greater sample size are needed to demonstrate its efficacy, especially in comparison to time-honored agents such as ondansetron. No adverse effects were noted in our limited study cohort.","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"11 1","pages":"155 - 160"},"PeriodicalIF":2.0,"publicationDate":"2019-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S221736","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44942449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Phase 1, Randomized, Double-Blind, Single-Dose, Placebo-Controlled Safety, Tolerability, And Pharmacokinetic/Pharmacodynamic Study Of Evolocumab In Healthy Chinese Subjects","authors":"Chao Liu, Hong Lu, Fei Yuan, Wei-li Chen, Hong-rong Xu, Hui Li, Cheng-Pang Hsu, O. Egbuna, Jihua Wu, C. Dias, Bassam Abosaleem, J. Rana, M. L. Monsalvo, Xuening Li, Zhigang Yu","doi":"10.2147/CPAA.S208033","DOIUrl":"https://doi.org/10.2147/CPAA.S208033","url":null,"abstract":"Purpose Evolocumab is a human monoclonal antibody that reduces circulating low-density lipoprotein cholesterol (LDL-C) by inhibiting proprotein convertase subtilisin/kexin type 9 (PCSK9). Data on evolocumab pharmacokinetics and pharmacodynamics are derived mostly from Caucasian populations. The objectives of this study were to characterize the single-dose pharmacokinetic and pharmacodynamic parameters, safety, and tolerability of evolocumab in healthy Chinese subjects. Subjects and methods This was a phase 1, randomized, double-blind, placebo-controlled study (CTR20150465). Two parallel cohorts were randomized 5:1 to receive single subcutaneous injections of either evolocumab (140 mg or 420 mg) or placebo. Pharmacokinetics, pharmacodynamics, and safety were evaluated through day 85. The primary endpoints were maximum concentration (Cmax) and area under the drug concentration–time curve from time 0 to time of last quantifiable concentration (AUClast). Results Thirty-six men (median age 26) were enrolled to receive evolocumab 140 mg (n=15), evolocumab 420 mg (n=15), or placebo (n=6). After 140 mg and 420 mg evolocumab, mean (SD) Cmax was 13.8 (3.6 μg/mL and 67.6 (15.2) μg/mL, respectively, and mean (SD) AUClast was 166 (55) day·μg/mL and 1110 (274) day·μg/mL, respectively. LDL-C declined reversibly, with reductions of 70% at 140 mg and 71% at 420 mg. Maximum effects on LDL-C and PCSK9 levels were reached by day 15 and 24 hrs, respectively, at 140 mg, and by day 22 and 4 hrs, respectively, at 420 mg. No serious adverse events occurred and the overall incidence of treatment-emergent adverse events was similar for evolocumab and placebo: 26.7% (140 mg) and 33.3% (placebo); 66.7% (420 mg) and 66.7% (placebo). Conclusion In this population of healthy Chinese subjects, single 140 mg and 420 mg doses of evolocumab exhibited nonlinear kinetics and more than dose-proportional increases in exposure, were associated with up to 71% reduction in LDL-C, and demonstrated a safety profile similar to placebo.","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"11 1","pages":"145 - 153"},"PeriodicalIF":2.0,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S208033","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42180962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamin B12 deficiency presenting as pseudo-thrombotic microangiopathy: a case report and literature review","authors":"Y. Fahmawi, Yesica Campos, M. Khushman, Omar Alkharabsheh, A. Manne, H. Zubair, Saadia Haleema, J. Polski, Sabrina Bessette","doi":"10.2147/CPAA.S207258","DOIUrl":"https://doi.org/10.2147/CPAA.S207258","url":null,"abstract":"Abstract Pseudo-thrombotic microangiopathy (pseudo-TMA) is a recognized, yet uncommon, clinical presentation of vitamin B12 deficiency. Patients with pseudo-TMA present with microangiopathic hemolytic anemia (MAHA), thrombocytopenia and schistocytes. They are often misdiagnosed as thrombotic thrombocytopenia purpura (TTP) and receive unnecessary therapy. Here, we report a case of a 60-year-old male who presented with thrombocytopenia and normocytic normochromic anemia. Anemia work-up was remarkable for severe B12 deficiency (<60 pg/mL) and a positive non-immune hemolysis panel. Peripheral smear was reviewed and showed anisocytes, poikilocytes, schistocytes and hypersegmented neutrophils. Vitamin B12 replacement (1000 mcg IM daily) was started, ADAMTS13 activity was sent and daily plasmapheresis was initiated. Over the next 3 days, the patient’s hemoglobin and platelets were stable and the hemolysis panel showed gradual improvement. On day 4, ADAMTS13 activity results came back normal at 61%. Accordingly, plasmapheresis was discontinued, parenteral B12 replacement was continued and that resulted in gradual improvement and eventually cessation of hemolysis and normalization of hemoglobin and platelets. In this patient, parietal cell autoantibodies were positive and so the diagnosis of pernicious anemia was made. Patients with severe vitamin B12 deficiency may present with features mimicking TTP such as MAHA, thrombocytopenia and schistocytosis. An early and accurate diagnosis of pseudo-TMA has a critical clinical impact with respect to administering the correct treatment with vitamin B12 replacement and avoiding, or shortening the duration of, unnecessary therapy with plasmapheresis.","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"11 1","pages":"127 - 131"},"PeriodicalIF":2.0,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S207258","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45734080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Approach to residual dizziness after successfully treated benign paroxysmal positional vertigo: effect of a polyphenol compound supplementation","authors":"A. Casani, E. Navari, R. Albera, G. Agus, G. Asprella Libonati, G. Chiarella, N. Lombardo, V. Marcelli, G. Ralli, L. Scotto di Santillo, R. Teggi, P. Viola, L. Califano","doi":"10.2147/CPAA.S210763","DOIUrl":"https://doi.org/10.2147/CPAA.S210763","url":null,"abstract":"Purpose To assess if a polyphenol compound supplementation (Vertigoval®) could improve residual dizziness earlier after benign paroxysmal positional vertigo (BPPV) and relieve patients from this disabling symptomatology. Methods In this prospective, multicentric study, 127 patients were randomized in the treatment group (TG), who received a 60-day supplementation, while 131 patients were randomized in the control group (CG), who did not receive any medication. The dizziness handicap inventory (DHI) score, static posturography, and the visual analog scale (VAS) for both dizziness (D-VAS) and nausea/vomit (N/V-VAS) were used as measures of outcome at baseline and after 30 and 60 days. Patients were asked about efficacy and tolerance to the treatment. Side effects were examined. Results A statistically significant greater decrease was established in the TG for DHI, D-VAS, and N/V-VAS compared to the CG. On the other hand, static posturography did not show statistical differences between the two groups, though a better clinical improvement after 60-day supplementation was shown in the TG in comparison to the CG. We counted mild side effects in only 2 patients. Most patients reported an excellent or good efficacy and tolerance to the treatment. Conclusion Residual dizziness is a frequent condition of unknown origin that manifests as persistent disabling imbalance after successful repositioning maneuvers for BPPV. The decreasing postural control can affect the quality of life, contributing to falling and psychological problems. The supplementation with the polyphenol compound used in our study is safe, manageable, and appeared to be able to reduce subjective symptoms and improve instability earlier, decreasing the risk of potential complications.","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"11 1","pages":"117 - 125"},"PeriodicalIF":2.0,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S210763","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43299371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioavailability and swallowability of an age-appropriate, delayed-release mesalamine formulation in healthy volunteers","authors":"Abhijeet S. Jakate, B. Mcnamee, Donald Burkindine","doi":"10.2147/CPAA.S193191","DOIUrl":"https://doi.org/10.2147/CPAA.S193191","url":null,"abstract":"Objective: Delayed-release mesalamine 400 mg capsules containing four 100 mg tablets have been developed for children with ulcerative colitis who have difficulty swallowing. Bioavailability of the mesalamine capsules was compared with existing mesalamine tablets in healthy adults, and the effect of food on bioavailability from mesalamine capsules was determined. Tablet swallowability in healthy children was evaluated. Methods: In the open-label, replicate-treatment, single-dose, crossover, comparative bioavailability study, healthy adult volunteers were randomized to one of four treatment sequences to receive mesalamine 400 mg tablets (fasted) twice, mesalamine 400 mg capsules (fasted) twice, and a mesalamine 400 mg capsule (with food) once, with ≥7 days between treatments. Pharmacokinetic (PK) parameters were calculated and analyzed using the reference-scaled average bioequivalence procedure. In the open-label, single-dose swallowability study, healthy children aged 5–11 years were asked to swallow eight placebo tablets identical to those contained in two mesalamine capsules. Results: In the bioavailability study (n=160), mesalamine capsules and tablets in fasted volunteers exhibited similarly delayed absorption and were shown to be bioequivalent; statistical parameters calculated from PK values met the criteria for bioequivalence. A slight increase in mesalamine bioavailability was observed with food administration, but the delayed-release performance of the capsules was not affected. Overall safety profiles between capsules and tablets were similar. In the swallowability study (n=60), the majority of children swallowed eight placebo tablets, with slight variability between age groups. Conclusion: Evaluation of PK parameters confirmed mesalamine capsules are bioequivalent to mesalamine tablets. Mesalamine capsules were well tolerated, can be administered with or without food, and are an age-appropriate product for children.","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"11 1","pages":"93 - 101"},"PeriodicalIF":2.0,"publicationDate":"2019-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S193191","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43223540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}