International journal of clinical pharmacology & toxicology最新文献

Hypoxia alters P-gp Expression and Activity in Three Different Rat Intestinal Modles: Implications for Levofloxacin Delivery 缺氧改变P-gp在三种不同大鼠肠道模型中的表达和活性：对左氧氟沙星给药的意义

International journal of clinical pharmacology & toxicology Pub Date : 2021-06-22 DOI: 10.19070/2167-910x-2100052

Y. Xi

引用次数: 0

CYP2B6 Genotype Guided Dosing of Propofol Anesthesia in the Elderly based on Nonparametric Population Pharmacokinetic Modeling and Simulations. 基于非参数人群药代动力学模型和模拟的CYP2B6基因型引导老年人给药异丙酚麻醉。

International journal of clinical pharmacology & toxicology Pub Date : 2017-01-01 DOI: 10.19070/2167-910X-1700041

A. Eugene

{"title":"CYP2B6 Genotype Guided Dosing of Propofol Anesthesia in the Elderly based on Nonparametric Population Pharmacokinetic Modeling and Simulations.","authors":"A. Eugene","doi":"10.19070/2167-910X-1700041","DOIUrl":"https://doi.org/10.19070/2167-910X-1700041","url":null,"abstract":"OBJECTIVE The primary aim of this article is to test the hypothesis that nonparametric pharmacometric modeling will accurately identify CYP2B6 genotype subgroups based on data from a study that reported results based on parametric pharmacokinetics (PK). METHODS Propofol concentration-time data were originally reported in the Kansaku et al. 2011 publication. Nonparametric Nonlinear Mixed Effects Modeling (NLME) was conducted using the PMETRICS R package while population pharmacokinetic model parameters were estimated using a FORTRAN compiler. Finally, model-based dosing simulations were conducted in the MATLAB Simbiology. RESULTS A total of 51 patients were included in the final PK analysis. A two-compartment gamma multiplicative error model adequately described the propofol concentration-time data. The precision of the goodness-of-fit plots resulted in an R2 of 0.927 and an R2 of 0.992 for the population prediction and individual predictions, respectively. Neither the UGT1A9 nor the CYP2B6 G516T gene variants resulted in statistically significant PK parameter differences while the CYP2B6 A785G gene variants resulted in statistically significant differences for the elimination rate. Model-based dosing-simulations comparing patients with the CYP2B6 AA & AG genotypes to both GG genotypes and patients from a multicenter trial suggest a 50% decrease in propofol infusion dose, to 25mg/kg/min, be made to result in approximately equivalent drug exposures. CONCLUSION Based on the pharmacometric modeling and simulation, if no dosage adjustments are made for the elderly CYP2B6 AA and AG genotypes, a 250% higher propofol blood exposure will be evident within 1-hour from the start of the infusion. Thus, based on the pharmacokinetic model, genotyping elderly patients for the CYP2B6 AA and AG gene variants will decrease the total propofol blood exposure during anesthesia and sedation when an infusion dose adjustment is made to 25mg/kg/min.","PeriodicalId":91507,"journal":{"name":"International journal of clinical pharmacology & toxicology","volume":"6 1 1","pages":"242-249"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68338016","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}

引用次数: 11

Identifying Treatment Response of Sertraline in a Teenager with Selective Mutism using Electrophysiological Neuroimaging. 应用电生理神经成像技术鉴别舍曲林治疗选择性缄默症的疗效。

International journal of clinical pharmacology & toxicology Pub Date : 2016-06-01 DOI: 10.19070/2167-910X-1600036

A. Eugene, J. Masiak

{"title":"Identifying Treatment Response of Sertraline in a Teenager with Selective Mutism using Electrophysiological Neuroimaging.","authors":"A. Eugene, J. Masiak","doi":"10.19070/2167-910X-1600036","DOIUrl":"https://doi.org/10.19070/2167-910X-1600036","url":null,"abstract":"BACKGROUND\u0000Selective Mutism is described as the inability to verbally express oneself in anxiety provoking social situations and may result in awkward social interactions in school-aged children. In this case-report we present the baseline electrophysiological neuroimaging results and after treatment with Sertraline for 6-weeks.\u0000\u0000\u0000METHODS\u0000A 20-channel EEG event-related potential recording was acquired during an internal voice task at baseline prior to the initiation of 50mg of Sertraline and then repeated 6-weeks after treatment with Sertraline. EEG signals were processed for movement, eye-blink, and muscle artifacts and ERP signal averaging was completed. ERPs were analyzed using Standard Low Resolution Brain Electromagnetic Tomography (sLORETA).\u0000\u0000\u0000RESULTS\u0000At baseline, Sertraline increased the neuronal activation in the middle temporal gyrus and the anterior cingulate gyrus from baseline in the patient following 6-weeks of treatment.\u0000\u0000\u0000CONCLUSION\u0000Our findings suggest that electrophysiological neuroimaging may provide a creative approach for personalizing medicine by providing insight to the pharmacodynamics of antidepressants.","PeriodicalId":91507,"journal":{"name":"International journal of clinical pharmacology & toxicology","volume":"5 4 1","pages":"216-219"},"PeriodicalIF":0.0,"publicationDate":"2016-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68337956","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}

引用次数: 5

Identifying Treatment Response of Sertraline in a Teenager with Selective Mutism using Electrophysiological Neuroimaging. 应用电生理神经成像技术鉴别舍曲林治疗选择性缄默症的疗效。

International journal of clinical pharmacology & toxicology Pub Date : 2016-06-01 Epub Date: 2016-06-15

Andy R Eugene, Jolanta Masiak

{"title":"Identifying Treatment Response of Sertraline in a Teenager with Selective Mutism using Electrophysiological Neuroimaging.","authors":"Andy R Eugene, Jolanta Masiak","doi":"","DOIUrl":"","url":null,"abstract":"Background: Selective Mutism is described as the inability to verbally express oneself in anxiety provoking social situations and may result in awkward social interactions in school-aged children. In this case-report we present the baseline electrophysiological neuroimaging results and after treatment with Sertraline for 6-weeks.Methods: A 20-channel EEG event-related potential recording was acquired during an internal voice task at baseline prior to the initiation of 50mg of Sertraline and then repeated 6-weeks after treatment with Sertraline. EEG signals were processed for movement, eye-blink, and muscle artifacts and ERP signal averaging was completed. ERPs were analyzed using Standard Low Resolution Brain Electromagnetic Tomography (sLORETA).Results: At baseline, Sertraline increased the neuronal activation in the middle temporal gyrus and the anterior cingulate gyrus from baseline in the patient following 6-weeks of treatment.Conclusion: Our findings suggest that electrophysiological neuroimaging may provide a creative approach for personalizing medicine by providing insight to the pharmacodynamics of antidepressants.","PeriodicalId":91507,"journal":{"name":"International journal of clinical pharmacology & toxicology","volume":"5 4","pages":"216-219"},"PeriodicalIF":0.0,"publicationDate":"2016-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4959607/pdf/nihms796654.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34322789","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}

引用次数: 0

Gender based Dosing of Metoprolol in the Elderly using Population Pharmacokinetic Modeling and Simulations. 基于性别的老年人美托洛尔给药的人群药代动力学模型和模拟。

International journal of clinical pharmacology & toxicology Pub Date : 2016-05-01 Epub Date: 2016-05-19

Andy R Eugene

{"title":"Gender based Dosing of Metoprolol in the Elderly using Population Pharmacokinetic Modeling and Simulations.","authors":"Andy R Eugene","doi":"","DOIUrl":"","url":null,"abstract":"Introduction: This article seeks to clarify if gender-based differences occur in the pharmacokinetics of metoprolol in the elderly patients. There are a series of physiologic changes that occur in the elderly ranging from decreased hepatic blood flow to increased adiposity causing higher plasma concentrations at therapeutic doses as compared to the healthy young population.Methods: Population pharmacokinetic modeling were performed using MONOLIX and Monte-Carlo simulations were conducted using MATLAB. The data was based from a previously published dataset where elderly patients, having multiple comorbidities, were administered a 50mg dose of metoprolol.Results: Metoprolol was modeled using a one-compartment model and resulted in the following population pharmacokinetic parameters: volume of distribution, V=38L (CV=155%), clearance rates, CL-Men=105L/hour and CL-Women=59.1L/hour (38%), time lag, Tlag=0.469 hour (CV=17%), and the absorption rate constant, Ka=0.235 hr-1 (CV=23%).Conclusion: Gender stratified doses resulting in an equivalent systemic metoprolol exposure in geriatric patients have been identified. Metoprolol doses resulting a similar AUC in a healthy young male administered 50mg tablet were 15mg for geriatric women and 25mg for geriatric men. Further, Metoprolol doses of 25mg for geriatric women and 50mg for geriatric men resulted in an equivalent AUC to a healthy young males dosed with a 100mg tablet. A 15mg Metoprolol tablet may need to be compounded to account for the gender differences in Metoprolol pharmacokinetics.","PeriodicalId":91507,"journal":{"name":"International journal of clinical pharmacology & toxicology","volume":"5 3","pages":"209-215"},"PeriodicalIF":0.0,"publicationDate":"2016-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4959610/pdf/nihms794156.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34322788","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}

引用次数: 0

Gender based Dosing of Metoprolol in the Elderly using Population Pharmacokinetic Modeling and Simulations. 基于性别的老年人美托洛尔给药的人群药代动力学模型和模拟。

International journal of clinical pharmacology & toxicology Pub Date : 2016-05-01 DOI: 10.19070/2167-910X-1600035

A. Eugene

{"title":"Gender based Dosing of Metoprolol in the Elderly using Population Pharmacokinetic Modeling and Simulations.","authors":"A. Eugene","doi":"10.19070/2167-910X-1600035","DOIUrl":"https://doi.org/10.19070/2167-910X-1600035","url":null,"abstract":"INTRODUCTION\u0000This article seeks to clarify if gender-based differences occur in the pharmacokinetics of metoprolol in the elderly patients. There are a series of physiologic changes that occur in the elderly ranging from decreased hepatic blood flow to increased adiposity causing higher plasma concentrations at therapeutic doses as compared to the healthy young population.\u0000\u0000\u0000METHODS\u0000Population pharmacokinetic modeling were performed using MONOLIX and Monte-Carlo simulations were conducted using MATLAB. The data was based from a previously published dataset where elderly patients, having multiple comorbidities, were administered a 50mg dose of metoprolol.\u0000\u0000\u0000RESULTS\u0000Metoprolol was modeled using a one-compartment model and resulted in the following population pharmacokinetic parameters: volume of distribution, V=38L (CV=155%), clearance rates, CL-Men=105L/hour and CL-Women=59.1L/hour (38%), time lag, Tlag=0.469 hour (CV=17%), and the absorption rate constant, Ka=0.235 hr-1 (CV=23%).\u0000\u0000\u0000CONCLUSION\u0000Gender stratified doses resulting in an equivalent systemic metoprolol exposure in geriatric patients have been identified. Metoprolol doses resulting a similar AUC in a healthy young male administered 50mg tablet were 15mg for geriatric women and 25mg for geriatric men. Further, Metoprolol doses of 25mg for geriatric women and 50mg for geriatric men resulted in an equivalent AUC to a healthy young males dosed with a 100mg tablet. A 15mg Metoprolol tablet may need to be compounded to account for the gender differences in Metoprolol pharmacokinetics.","PeriodicalId":91507,"journal":{"name":"International journal of clinical pharmacology & toxicology","volume":"5 3 1","pages":"209-215"},"PeriodicalIF":0.0,"publicationDate":"2016-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68337879","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}

引用次数: 20

AT₂ receptor: Its role in obesity associated hypertension. AT2受体在肥胖相关性高血压中的作用

International journal of clinical pharmacology & toxicology Pub Date : 2012-10-01 Epub Date: 2012-10-16 DOI: 10.19070/2167-910X-120003

Quaisar Ali, Tahir Hussain

{"title":"AT2 receptor: Its role in obesity associated hypertension.","authors":"Quaisar Ali, Tahir Hussain","doi":"10.19070/2167-910X-120003","DOIUrl":"https://doi.org/10.19070/2167-910X-120003","url":null,"abstract":"The renin-angiotensin system (RAS) is a hormonal cascade that acts together to regulate blood pressure. Angiotensin II (Ang II) is the major octapeptide of RAS and mediates its cellular and physiological actions by acting on AT1 and AT2 receptor. Most of the cellular and physiological actions of Ang II such as cellular growth and proliferation, vasoconstriction, antinatriuresis and increase in blood pressure are mediated via AT1 receptor. The functions associated with the AT2 receptors are less studied, in part, due to its lower expression in adult tissues. However, AT2 receptor has been suggested as functional antagonist of AT1 receptors and thereby opposes the actions of Ang II mediated via AT1 receptor. Thus, the activation of AT2 receptors has been shown to cause vasodilatation, natriuresis and decrease in blood pressure. After the discovery of the AT2 receptor in various parts of the kidney, including in proximal tubules, there has been an interest in establishing a link between the renal AT2 receptor, renal Na-excretion and blood pressure regulation. Earlier, we have reported that activation of renal AT2 receptors increases urinary Na excretion in obese Zucker rats, in part via inhibiting Na+/K+- ATPase (NKA) activity and stimulating nitric oxide/cGMP pathway in the proximal tubules. An impaired pressure natriuresis and increased AT1 receptor function is believed to be the cause of hypertension in obese Zucker rats and other animal models of obesity. In this review, we are focussing on the role of renin angiotensin system especially AT2 receptors in obesity associated hypertension.","PeriodicalId":91507,"journal":{"name":"International journal of clinical pharmacology & toxicology","volume":"1 1","pages":"15-19"},"PeriodicalIF":0.0,"publicationDate":"2012-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004927/pdf/nihms811995.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34358240","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}

引用次数: 1