Clinical Pharmacology : Advances and Applications最新文献

{"title":"The Effect of Moderate- and High-Fat Meals on the Bioavailability of Dolutegravir/Rilpivirine Fixed-Dose Combination Tablet.","authors":"Rashmi Mehta,&nbsp;Joseph Piscitelli,&nbsp;Allen Wolstenholme,&nbsp;Caifeng Fu,&nbsp;Herta Crauwels,&nbsp;Brian Wynne,&nbsp;Kimberly Adkison","doi":"10.2147/CPAA.S250751","DOIUrl":"https://doi.org/10.2147/CPAA.S250751","url":null,"abstract":"<p><p>Dolutegravir 50 mg (DTG) and rilpivirine 25 mg (RPV) are a newly approved 2-drug regimen for the treatment of HIV in virally suppressed patients. A 2-part study evaluated the relative bioavailability and food effect of five experimental fixed-dose combination (FDC) tablet formulations of DTG/RPV. When given with a moderate- or high-fat meal, the absorption of both DTG and RPV was increased, resulting in higher exposures. As per product labelling, DTG/RPV FDC should be taken with a meal.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"12 ","pages":"49-52"},"PeriodicalIF":2.0,"publicationDate":"2020-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S250751","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38108969","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":"The Parkinson's Disease Death Rate: Carbidopa and Vitamin B6 [Expression of Concern].","authors":"","doi":"10.2147/CPAA.S240231","DOIUrl":"https://doi.org/10.2147/CPAA.S240231","url":null,"abstract":"","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"12 ","pages":"43"},"PeriodicalIF":2.0,"publicationDate":"2020-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S240231","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37949473","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":"Administration of Supplemental L-Tyrosine with Phenelzine: A Clinical Literature Review [Expression of Concern].","authors":"","doi":"10.2147/CPAA.S240229","DOIUrl":"https://doi.org/10.2147/CPAA.S240229","url":null,"abstract":"","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"12 ","pages":"47"},"PeriodicalIF":2.0,"publicationDate":"2020-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S240229","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37949475","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":"Parkinson's Disease: Carbidopa, Nausea, and Dyskinesia [Expression of Concern].","authors":"","doi":"10.2147/CPAA.S240233","DOIUrl":"https://doi.org/10.2147/CPAA.S240233","url":null,"abstract":"","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"12 ","pages":"45"},"PeriodicalIF":2.0,"publicationDate":"2020-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S240233","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37949474","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":"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}