Journal of clinical pharmacology最新文献

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Effect of multiple intravenous doses of lanicemine (AZD6765) on the pharmacokinetics of midazolam in healthy subjects. 多剂量静脉注射lanicemine (AZD6765)对健康人咪达唑仑药代动力学的影响
IF 2.9 4区 医学
Journal of clinical pharmacology Pub Date : 2015-09-01 Epub Date: 2015-06-02 DOI: 10.1002/jcph.515
Khanh H Bui, Diansong Zhou, Felix Agbo, Jian Guo
{"title":"Effect of multiple intravenous doses of lanicemine (AZD6765) on the pharmacokinetics of midazolam in healthy subjects.","authors":"Khanh H Bui,&nbsp;Diansong Zhou,&nbsp;Felix Agbo,&nbsp;Jian Guo","doi":"10.1002/jcph.515","DOIUrl":"https://doi.org/10.1002/jcph.515","url":null,"abstract":"<p><p>The objectives of the present study were to evaluate safety and tolerability as well as the effects of multiple doses of lanicemine on the pharmacokinetics of a CYP3A substrate, midazolam. A total of 46 healthy volunteers were enrolled in the open-label, fixed-sequence, nonrandomized study. All volunteers received an oral dose of 5 mg of midazolam alone or after 6 days of 150 mg daily intravenous infusion of lanicemine. Lanicemine reached a plasma Cmax of 1.51 μg/mL after 150 mg daily dosing to steady state. The geometric mean CL, Vss, and t1/2 of lanicemine were 8.1 L/h, 122.0 L, and 10.4 hours, respectively. The geometric least-squares mean ratios and 90% confidence intervals for midazolam AUC0- ∞ , and Cmax were within the 80% to 125% limits when lanicemine plus midazolam treatment was compared with midazolam alone, demonstrating that daily dosing with 150 mg of lanicemine for 6 days had no effect on CYP3A activity. Comprehensive physiologically based pharmacokinetic modeling using in vitro and in silico findings also indicated lanicemine would have little impact on the pharmacokinetics of CYP3A substrate, such as midazolam. In addition, lanicemine and midazolam administered alone or in combination were generally safe and well tolerated. </p>","PeriodicalId":15536,"journal":{"name":"Journal of clinical pharmacology","volume":"55 9","pages":"1024-30"},"PeriodicalIF":2.9,"publicationDate":"2015-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jcph.515","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33103912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 6
Meta-analysis of short-term high versus low doses of atorvastatin preventing contrast-induced acute kidney injury in patients undergoing coronary angiography/percutaneous coronary intervention. 短期高剂量与低剂量阿托伐他汀预防冠脉造影/经皮冠状动脉介入治疗患者造影剂引起的急性肾损伤的meta分析
IF 2.9 4区 医学
Journal of clinical pharmacology Pub Date : 2015-02-01 Epub Date: 2015-01-05 DOI: 10.1002/jcph.411
Hongjiang Wu, Dongmei Li, Minhua Fang, Hongguang Han, Huishan Wang
{"title":"Meta-analysis of short-term high versus low doses of atorvastatin preventing contrast-induced acute kidney injury in patients undergoing coronary angiography/percutaneous coronary intervention.","authors":"Hongjiang Wu,&nbsp;Dongmei Li,&nbsp;Minhua Fang,&nbsp;Hongguang Han,&nbsp;Huishan Wang","doi":"10.1002/jcph.411","DOIUrl":"https://doi.org/10.1002/jcph.411","url":null,"abstract":"<p><p>This study aimed to investigate the impact of different doses of atorvastatin on contrast-induced acute kidney injury (CI-AKI) in patients undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI) requiring contrast media by performing a meta-analysis. We searched the PubMed, EMBASE, Cochrane Library, Wanfang database, China National Knowledge Infrastructure, and VIP database through April 2014. Only randomized controlled trials (RCTs) comparing short-term high-dose atorvastatin with low-dose atorvastatin on CI-AKI were selected. The main outcomes were the change of acute kidney injury markers and the incidence of contrast-induced nephropathy (CIN). We combined 14 RCTs consisting of 1,689 patients. Compared with the low-dose atorvastatin, high-dose atorvastatin treatment was associated with a reduction in serum creatinine levels (weighted mean differences [WMD]-0.1 mg/dL; 95%CI -0.14 to -0.05). In addition, high-dose atorvastatin treatment was also associated with a lower incidence of CIN (risk ratios 0.41; 95%CI 0.29-0.56). This meta-analysis suggests that short-term high-dose atorvastatin therapy appears to be superior to the low-dose atorvastatin in preventing CI-AKI among patients undergoing CAG/PCI requiring contrast media. </p>","PeriodicalId":15536,"journal":{"name":"Journal of clinical pharmacology","volume":"55 2","pages":"123-31"},"PeriodicalIF":2.9,"publicationDate":"2015-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jcph.411","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32743395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 17
Potential drug-drug interactions in cardiothoracic intensive care unit of a pulmonary teaching hospital. 某肺科教学医院心胸重症监护病房潜在的药物-药物相互作用
IF 2.9 4区 医学
Journal of clinical pharmacology Pub Date : 2015-02-01 Epub Date: 2014-12-05 DOI: 10.1002/jcph.421
Behrooz Farzanegan, Maryam Alehashem, Marjan Bastani, Shadi Baniasadi
{"title":"Potential drug-drug interactions in cardiothoracic intensive care unit of a pulmonary teaching hospital.","authors":"Behrooz Farzanegan,&nbsp;Maryam Alehashem,&nbsp;Marjan Bastani,&nbsp;Shadi Baniasadi","doi":"10.1002/jcph.421","DOIUrl":"https://doi.org/10.1002/jcph.421","url":null,"abstract":"<p><p>Little is known about clinically significant drug-drug interactions (DDIs) in respiratory settings. DDIs are more likely to occur in critically ill patients due to complex pharmacotherapy regimens and organ dysfunctions. The aim of this study was to identify the pattern of potential DDIs (pDDIs) occurring in cardiothoracic intensive care unit (ICU) of a pulmonary hospital. A prospective observational study was conducted for 6 months. All pDDIs for admitted patients in cardiothoracic ICU were identified with Lexi-Interact program and assessed by a clinical pharmacologist. The interacting drugs, reliability, mechanisms, potential outcomes, and clinical management were evaluated for severe and contraindicated interactions. The study included 195 patients. Lung cancer (14.9%) was the most common diagnosis followed by tracheal stenosis (14.3%). The rate of pDDIs was 720.5/100 patients. Interactions were more commonly observed in transplant patients. 17.7% of pDDIs were considered as severe and contraindicated interactions. Metabolism (54.8%) and additive (24.2%) interactions were the most frequent mechanisms leading to pDDIs, and azole antifungals and fluoroquinolones were the main drug classes involved. The pattern of pDDIs in cardiothoracic ICU differs from other ICU settings. Specialized epidemiological knowledge of drug interactions may help clinical practitioners to reduce the risk of adverse drug events. </p>","PeriodicalId":15536,"journal":{"name":"Journal of clinical pharmacology","volume":"55 2","pages":"132-6"},"PeriodicalIF":2.9,"publicationDate":"2015-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jcph.421","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32792055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 19
Pharmacokinetics and pharmacodynamics of a polyethylene glycol (PEG)-conjugated GLP-receptor agonist once weekly in Chinese patients with type 2 diabetes. 聚乙二醇偶联glp受体激动剂在中国2型糖尿病患者中的药代动力学和药效学
IF 2.9 4区 医学
Journal of clinical pharmacology Pub Date : 2015-02-01 Epub Date: 2014-11-03 DOI: 10.1002/jcph.386
Guang-Ran Yang, Xiu-Li Zhao, Fan Jin, Li-Hong Shi, Jin-Kui Yang
{"title":"Pharmacokinetics and pharmacodynamics of a polyethylene glycol (PEG)-conjugated GLP-receptor agonist once weekly in Chinese patients with type 2 diabetes.","authors":"Guang-Ran Yang,&nbsp;Xiu-Li Zhao,&nbsp;Fan Jin,&nbsp;Li-Hong Shi,&nbsp;Jin-Kui Yang","doi":"10.1002/jcph.386","DOIUrl":"https://doi.org/10.1002/jcph.386","url":null,"abstract":"<p><p>This multi-center, randomized, double-blind, multiple dose-escalation study was conducted to assess the pharmacokinetics and pharmacodynamics of a newly developed polyethylene glycol (PEG)-conjugated glucagon-like peptide-1 (GLP-1) receptor agonist, PEX168 once weekly in Chinese patients with type 2 diabetes (T2DM). Fifty patients aged 20-65 years, either treatment-naive or having been treated with single oral antidiabetic agents were eligible. Antidiabetic agents were stopped for 14 days before the study was initiated. Patients were allocated randomly into groups with subcutaneous PEX168 or placebo once-weekly for 8 weeks followed by 6 weeks observation. From baseline to 8 weeks, HbA1c were decreased by up to 0.0, 0.2, 0.6, 0.9, and -0.4% in the 50, 100, 200, 300 μg PEX168 groups, and placebo group respectively. The mean elimination half-life of PEX168 was 131.8-139.8 hours. The mean tmax was 67.3 hours. Steady-state plasma PEX168 concentrations were attained after 4 weeks. PEX168 once-weekly were tolerable by the patients: adverse effects reported ranged from 'mild' to 'moderate'. The most frequent drug-related adverse effects were nausea, vomiting, and diarrhea of mild to moderate severity. Administration of the PEG-conjugated GLP-1 receptor agonist PEX168 resulted in dose-proportional pharmacokinetic and antidiabetic pharmacodynamic activity. </p>","PeriodicalId":15536,"journal":{"name":"Journal of clinical pharmacology","volume":"55 2","pages":"152-8"},"PeriodicalIF":2.9,"publicationDate":"2015-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jcph.386","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32622609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 16
Comparison of the administration of teneligliptin every day versus every other day in Japanese patients with type 2 diabetes: a randomized non-inferior test. 日本2型糖尿病患者每日与隔日给药替尼格列汀的比较:一项随机非劣效试验
IF 2.9 4区 医学
Journal of clinical pharmacology Pub Date : 2015-02-01 Epub Date: 2014-09-07 DOI: 10.1002/jcph.385
Kazunari Kamiko, Kazutaka Aoki, Hiroshi Kamiyama, Masataka Taguri, Eriko Shibata, Yumiko Ashiya, Fuyuki Minagawa, Kazuaki Shinoda, Shigeru Nakajima, Yasuo Terauchi
{"title":"Comparison of the administration of teneligliptin every day versus every other day in Japanese patients with type 2 diabetes: a randomized non-inferior test.","authors":"Kazunari Kamiko,&nbsp;Kazutaka Aoki,&nbsp;Hiroshi Kamiyama,&nbsp;Masataka Taguri,&nbsp;Eriko Shibata,&nbsp;Yumiko Ashiya,&nbsp;Fuyuki Minagawa,&nbsp;Kazuaki Shinoda,&nbsp;Shigeru Nakajima,&nbsp;Yasuo Terauchi","doi":"10.1002/jcph.385","DOIUrl":"https://doi.org/10.1002/jcph.385","url":null,"abstract":"<p><p>The half life (t1/2 ) of teneligliptin is 24.2 hours. Accordingly, we hypothesized that the administration of teneligliptin every other day might improve glycemic control. In this study, we evaluated the effectiveness of the administration of teneligliptin every other day in Japanese patients with type 2 diabetes. Fifty-one patients were randomly assigned to receive treatment with 20 mg of teneligliptin every day (Group A) or 20 mg of teneligliptin every other day (Group B) for 12 weeks. HbA1c, glycoalbumin (GA), 1,5-anhydroglucitol (1,5-AG), lipid, blood pressure, body weight, urine albumin-to-creatinine ratio, overall treatment satisfaction level, adverse events and drug adherence were all measured. Forty-seven patients completed this study, and the HbA1c, GA, and 1,5-AG levels in group B were found to be decreased to the same extent as those in group A. No distinct differences in the overall treatment satisfaction level, adverse events, or drug adherence were seen between the two groups at 12 weeks. The administration of teneligliptin every other day had a similar efficacy, patient satisfaction level, and safety compared with its administration every day. This information will be useful for reducing the economic load without changing the patients' satisfaction and glycemic control. </p>","PeriodicalId":15536,"journal":{"name":"Journal of clinical pharmacology","volume":"55 2","pages":"144-51"},"PeriodicalIF":2.9,"publicationDate":"2015-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jcph.385","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32616014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 5
Pharmacokinetics of hydrocodone/acetaminophen combination product in children ages 6-17 with moderate to moderately severe postoperative pain. 氢可酮/对乙酰氨基酚联合产品在6-17岁中重度术后疼痛患儿中的药代动力学
IF 2.9 4区 医学
Journal of clinical pharmacology Pub Date : 2015-02-01 Epub Date: 2014-09-26 DOI: 10.1002/jcph.394
Wei Liu, Sandeep Dutta, Greg Kearns, Walid Awni, Kathleen A Neville
{"title":"Pharmacokinetics of hydrocodone/acetaminophen combination product in children ages 6-17 with moderate to moderately severe postoperative pain.","authors":"Wei Liu,&nbsp;Sandeep Dutta,&nbsp;Greg Kearns,&nbsp;Walid Awni,&nbsp;Kathleen A Neville","doi":"10.1002/jcph.394","DOIUrl":"https://doi.org/10.1002/jcph.394","url":null,"abstract":"<p><p>Lortab® Elixir, a proprietary combination product containing hydrocodone and acetaminophen, is approved in the US for the treatment of moderate to moderately severe pain in children. Despite this approval, pediatric pharmacokinetic data using this product have not been previously published. Using a single-dose open-label study approach, we evaluated the pharmacokinetics, tolerability, and safety of this product in 17 healthy children 6-17 years of age. Results showed that the body weight-normalized oral clearance (L/h/kg) of hydrocodone and acetaminophen were 42% and 27% higher, respectively when compared to data from healthy adults. This suggests that a higher mg/kg dose would be required in children to achieve exposures similar to adults. We found adjustment of hydrocodone and acetaminophen dose by body surface area to be more optimal than body weight-based dose adjustments for achieving similar systemic exposure in children and adults. However, body weight-based hydrocodone and acetaminophen dosing regimens provided close approximation of adult exposures in pediatric patients with approximately 22% to 24% lower hydrocodone and acetaminophen dose/BW-normalized AUC in pediatric patients compared to adults. Finally, the adverse event profile in our pediatric cohort was consistent with that expected of opioid-naive subjects receiving opioid-combination therapy. </p>","PeriodicalId":15536,"journal":{"name":"Journal of clinical pharmacology","volume":"55 2","pages":"204-11"},"PeriodicalIF":2.9,"publicationDate":"2015-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jcph.394","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32647832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 8
Pediatric vancomycin dosing: Trends over time and the impact of therapeutic drug monitoring. 儿童万古霉素剂量:随时间的趋势和治疗药物监测的影响。
IF 2.9 4区 医学
Journal of clinical pharmacology Pub Date : 2015-02-01 Epub Date: 2014-11-07 DOI: 10.1002/jcph.402
Alfred H Balch, Jonathan E Constance, Emily A Thorell, Chris Stockmann, Ernest K Korgenski, Sarah C Campbell, Michael G Spigarelli, Catherine M T Sherwin
{"title":"Pediatric vancomycin dosing: Trends over time and the impact of therapeutic drug monitoring.","authors":"Alfred H Balch,&nbsp;Jonathan E Constance,&nbsp;Emily A Thorell,&nbsp;Chris Stockmann,&nbsp;Ernest K Korgenski,&nbsp;Sarah C Campbell,&nbsp;Michael G Spigarelli,&nbsp;Catherine M T Sherwin","doi":"10.1002/jcph.402","DOIUrl":"https://doi.org/10.1002/jcph.402","url":null,"abstract":"<p><p>Monitoring of vancomycin trough concentrations is recommended for pediatric patients in the product label and by several professional societies. However, among a network of freestanding children's hospitals vancomycin therapeutic drug monitoring (TDM) practices were reported to be highly variable. In this study, we sought to evaluate whether trends in vancomycin use and TDM changed across a large healthcare delivery system in Utah and Idaho from 2006 to 2012. Children ≤18 years who received ≥2 vancomycin doses were included. Overall, vancomycin TDM was performed during 5,035 (80%) of 6,259 hospital encounters, in which 85,442 doses were administered and 7,935 concentrations were obtained. Across this time period, the median trough concentration increased from 10.9 to 13.7 µg/mL (P < .001), which temporally coincided with recommendations published by the Infectious Disease Society of America that recommend targeting higher trough concentrations. Two or more abnormally low trough concentrations were accompanied by an increase in the dose 75% of the time. Similarly, ≥2 abnormally high trough concentrations were followed by a decrease in the dose 35% of the time. In aggregate, these data suggest that vancomycin TDM is commonly performed among children and the majority of abnormal trough concentrations were associated with an appropriate modification to the dosing regimen. </p>","PeriodicalId":15536,"journal":{"name":"Journal of clinical pharmacology","volume":"55 2","pages":"212-20"},"PeriodicalIF":2.9,"publicationDate":"2015-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jcph.402","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32703794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 21
Dose escalation pharmacokinetics of intranasal scopolamine gel formulation. 鼻内东莨菪碱凝胶制剂剂量递增药代动力学研究。
IF 2.9 4区 医学
Journal of clinical pharmacology Pub Date : 2015-02-01 Epub Date: 2014-12-05 DOI: 10.1002/jcph.391
Lei Wu, Jason L Boyd, Vernie Daniels, Zuwei Wang, Diana S-L Chow, Lakshmi Putcha
{"title":"Dose escalation pharmacokinetics of intranasal scopolamine gel formulation.","authors":"Lei Wu,&nbsp;Jason L Boyd,&nbsp;Vernie Daniels,&nbsp;Zuwei Wang,&nbsp;Diana S-L Chow,&nbsp;Lakshmi Putcha","doi":"10.1002/jcph.391","DOIUrl":"https://doi.org/10.1002/jcph.391","url":null,"abstract":"<p><p>Astronauts experience Space Motion Sickness requiring treatment with an anti-motion sickness medication, scopolamine during space missions. Bioavailability after oral administration of scopolamine is low and variable, and absorption form transdermal patch is slow and prolonged. Intranasal administration achieves faster absorption and higher bioavailability of drugs that are subject to extrahepatic, first pass metabolism after oral dosing. We examined pharmacokinetics of 0.1, 0.2, and 0.4 mg doses of the Investigational New Drug formulation of intranasal scopolamine gel (INSCOP) in 12 healthy subjects using a randomized, double-blind cross-over study design. Subjects received one squirt of 0.1 g of gel containing either 0.1 mg or 0.2 mg/0.1 mL scopolamine or placebo in each nostril. Serial blood samples and total urine voids were collected after dosing and drug concentrations were determined using a modified LC-MS-MS method. Results indicate dose-linear pharmacokinetics of scopolamine with linear increases in Cmax and AUC within the dose range tested. Plasma drug concentrations were significantly lower in females than in males after administration of 0.4 dose. All three doses were well tolerated with no unexpected or serious adverse side effects reported. These results suggest that intranasal scopolamine gel formulation (INSCOP) offers a fast, reliable, and safe alternative for the treatment of motion sickness. </p>","PeriodicalId":15536,"journal":{"name":"Journal of clinical pharmacology","volume":"55 2","pages":"195-203"},"PeriodicalIF":2.9,"publicationDate":"2015-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jcph.391","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32639124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 4
Population pharmacokinetics of ceftolozane/tazobactam in healthy volunteers, subjects with varying degrees of renal function and patients with bacterial infections. 头孢妥仑/他唑巴坦在健康志愿者、不同程度肾功能受试者和细菌感染患者中的群体药代动力学。
IF 2.9 4区 医学
Journal of clinical pharmacology Pub Date : 2015-02-01 Epub Date: 2014-11-14 DOI: 10.1002/jcph.395
Gurudatt Chandorkar, Alan Xiao, Mohamad-Samer Mouksassi, Ellie Hershberger, Gopal Krishna
{"title":"Population pharmacokinetics of ceftolozane/tazobactam in healthy volunteers, subjects with varying degrees of renal function and patients with bacterial infections.","authors":"Gurudatt Chandorkar, Alan Xiao, Mohamad-Samer Mouksassi, Ellie Hershberger, Gopal Krishna","doi":"10.1002/jcph.395","DOIUrl":"10.1002/jcph.395","url":null,"abstract":"<p><p>Ceftolozane/tazobactam is a novel antipseudomonal cephalosporin and β-lactamase inhibitor in clinical development for treatment of complicated urinary tract (cUTI) and intra-abdominal (cIAI) infections and nosocomial pneumonia. The population pharmacokinetics of ceftolozane/tazobactam were characterized in healthy volunteers, subjects with varying degrees of renal function, and patients with cIAI or cUTI. Serum concentration data from 376 adults who received ceftolozane/tazobactam in doses ranging from 500 to 3000 mg were analyzed to identify factors contributing to the pharmacokinetic variability. Ceftolozane/tazobactam pharmacokinetics were well described by a linear two-compartment model with first-order elimination and moderate between-subject variability in both clearance and volume of distribution (Vc). For both ceftolozane and tazobactam, clearance was highly correlated with renal function with creatinine clearance influencing exposure, and infection influencing Vc. Body weight was an additional covariate affecting the Vc of ceftolozane. Other covariates tested, such as age, body weight, sex, ethnicity, and presence of infection, had no clinically relevant effects on exposure. The final pharmacokinetic models adequately described the plasma concentrations of ceftolozane and tazobactam and form the basis for further modeling and simulation including evaluation of probability of target attainment in a diverse population with varying demographics, degrees of renal function, and infection status. </p>","PeriodicalId":15536,"journal":{"name":"Journal of clinical pharmacology","volume":"55 2","pages":"230-9"},"PeriodicalIF":2.9,"publicationDate":"2015-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7f/92/jcph0055-0230.PMC4303958.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32647763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Non-obligatory role of prostaglandin D2 receptor subtype 1 in rosacea: laropiprant in comparison to a placebo did not alleviate the symptoms of erythematoelangiectaic rosacea. 前列腺素D2受体亚型1在酒渣鼻中的非强制性作用:与安慰剂相比,laropiprant并没有减轻红斑性血管扩张型酒渣鼻的症状。
IF 2.9 4区 医学
Journal of clinical pharmacology Pub Date : 2015-02-01 Epub Date: 2014-09-04 DOI: 10.1002/jcph.383
Rajesh Krishna, Ying Guo, Valerie Schulz, Evyan Cord-Cruz, Shanna Smith, Suzanne Hair, Walter K Nahm, Zoe D Draelos
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引用次数: 5
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