Abstract：
:Precision medicine in oncology is the result of an increasing awareness of patient-specific clinical features coupled with the development of genomic-based diagnostics and targeted therapeutics. Companion diagnostics designed for specific drug-target pairs were the first to widely utilize clinically applicable tumor biomarkers (eg, HER2, EGFR), directing treatment for patients whose tumors exhibit a mutation susceptible to an FDA-approved targeted therapy (eg, trastuzumab, erlotinib). Clinically relevant germline mutations in drug-metabolizing enzymes and transporters (eg, TPMT, DPYD) have been shown to impact drug response, providing a rationale for individualized dosing to optimize treatment. The use of multigene expression-based assays to analyze an array of prognostic biomarkers has been shown to help direct treatment decisions, especially in breast cancer (eg, Oncotype DX). More recently, the use of next-generation sequencing to detect many potential "actionable" cancer molecular alterations is further shifting the 1 gene-1 drug paradigm toward a more comprehensive, multigene approach. Currently, many clinical trials (eg, NCI-MATCH, NCI-MPACT) are assessing novel diagnostic tools with a combination of different targeted therapeutics while also examining tumor biomarkers that were previously unexplored in a variety of cancer histologies. Results from ongoing trials such as the NCI-MATCH will help determine the clinical utility and future development of the precision-medicine approach.
journal_name
J Clin Pharmacoljournal_title
Journal of clinical pharmacologyauthors
Schmidt KT,Chau CH,Price DK,Figg WDdoi
10.1002/jcph.765subject
Has Abstractpub_date
2016-12-01 00:00:00pages
1484-1499issue
12eissn
0091-2700issn
1552-4604journal_volume
56pub_type
杂志文章,评审abstract：:The pharmacokinetics of exogenously administered DHEA have not been well characterized despite its increasing use in therapeutic and research investigations. The purpose of this study was to evaluate the pharmacokinetics of DHEA and its sulfated metabolite (DHEA-S) after single- and multiple-dose oral administration o...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：
更新日期：2000-06-01 00:00:00
abstract：:Numerous physiologic variations, including urinary protein excretion, low serum albumin concentrations, and reductions in kidney function (clearance), exist in patients with glomerulonephritis. These factors could alter the disposition of numerous drugs. The purpose of the current article was to review the influence o...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1177/0091270011413895
更新日期：2012-01-01 00:00:00
abstract：:The chemoattractant receptor-homologous molecule expressed on T-helper 2 cells (CRTH2) is a G-protein-coupled receptor for prostaglandin D2 , a key mediator in inflammatory disorders. In this randomized, double-blind, placebo-controlled study we investigated the single- and multiple-dose tolerability, pharmacokinetics...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1002/jcph.478
更新日期：2015-07-01 00:00:00
abstract：:The isoproterenol sensitivity (dose-response curve) and the total body clearance of propranolol were measured in 80 men including 15 normal subjects and 65 essential hypertensive patients (20 borderline and 45 permanent hypertensives). The critical dose of isoproterenol was found to be directly correlated to weight (P...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1976.tb01514.x
更新日期：1976-04-01 00:00:00
abstract：:Semagacestat, a γ-secretase inhibitor, reduces formation of amyloid beta peptide. Two single-dose (140 mg), open-label, randomized, 3-period, crossover studies evaluated the effect of formulation, food, and time of dosing on the pharmacokinetics and pharmacodynamics of semagacestat in healthy participants. The first s...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1177/0091270011407195
更新日期：2012-06-01 00:00:00
abstract：:The objective of this study was to measure the steady-state cerebrospinal fluid (CSF) concentration of LY450108 and LY451395 (positive modulators of AMPA receptors) in healthy subjects after the administration of 1 mg and 5 mg. Secondary objectives included the evaluation of safety, pharmacokinetics, and steady-state ...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1177/0091270006286899
更新日期：2006-04-01 00:00:00
abstract：:Tinidazole is a potent nitroimidazole compound active against, and used to treat, Trichomonas vaginalis infections in males and females. Speculation exists in the literature that observed differences in tinidazole plasma concentrations between males and females may be due to sex-mediated pharmacokinetic differences. T...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1982.tb02650.x
更新日期：1982-11-01 00:00:00
abstract：:Due to the prevalence of both gastrointestinal and cardiovascular diseases, it is likely that patients may be coprescribed gastric parietal cell proton pump inhibitors and beta-adrenergic antagonists. Therefore, the objectives of this phase I study were to assess the potential effects of the coadministration of lansop...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1177/00912700022008856
更新日期：2000-03-01 00:00:00
abstract：:Research into the distribution of medication errors usually focuses on isolated stages within the medication use process. Our study aimed to provide a novel process-oriented approach to medication incident analysis focusing on medication error chains. Our study was conducted across a 900-bed teaching hospital in Switz...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.319
更新日期：2014-10-01 00:00:00
abstract：:Varenicline is a novel selective α4β2 nicotinic acetylcholine partial agonist developed for smoking cessation. Single- and multiple dose studies were conducted to investigate pharmacokinetics, safety, and tolerability of varenicline in healthy male Japanese smokers. The single-dose study was conducted as a double-blin...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1177/0091270010372388
更新日期：2011-04-01 00:00:00
abstract：:Cyclophosphamide-based regimens are front-line treatment for numerous pediatric malignancies; however, current dosing methods result in considerable interpatient variability in tumor response and toxicity. In this pediatric population, the authors' objectives were (1) to quantify and explain the pharmacokinetic variab...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,多中心研究
doi：10.1177/0091270008325928
更新日期：2009-01-01 00:00:00
abstract：:The frequency of hemodialysis-associated hemorrhage was studied prospectively in two successive, parallel, heparin-controlled studies using epoprostenol (PGI2; average dose, 4.1 ng/kg.min) as the sole antithrombotic agent. Sixty-three patients with active or recently active bleeding underwent 163 hemodialysis treatmen...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1988.tb03222.x
更新日期：1988-09-01 00:00:00
abstract：:The Cardiac Antiarrhythmic Suppression Trial (CAST) showed flecainide and encainide induced excess mortality compared with placebo. Labeling drugs as Class 1C is based on clinical observations, comprising measurements of the electrocardiographic parameters QRS. H-V and J-T intervals and of effective refractory period ...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1002/j.1552-4604.1991.tb03695.x
更新日期：1991-02-01 00:00:00
abstract：:The aim of this study was to test the usefulness of the metabolite/caffeine ratio for the evaluation of hepatic dysfunction. Subjects with liver cirrhosis and chronic hepatitis, as well as healthy volunteers, were given the oral dose of 300 mg caffeine. Blood samples were collected after 4, 8, and 12 hours. Concentrat...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1177/0091270004263468
更新日期：2004-04-01 00:00:00
abstract：:Epoxieicosatrienoic acids (EETs) play a protective role against damaging processes in the kidney. We have assessed the effect of polymorphisms in EETs-producing enzymes (CYP2C8 and CYP2J2) and other proteins involved in calcineurin inhibitors (CNIs) disposition (CYP3A4, CYP3A5, and ABCB1) on graft function and clinica...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.15
更新日期：2013-04-01 00:00:00
abstract：:Data from 60 patients treated with amikacin were analyzed for factors associated with nephrotoxicity. In 42 of these patients, data were examined for factors associated with clinical outcome. Variables evaluated included patient weight, age, sex, serum creatinine level, creatinine clearance, duration of therapy, total...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1986.tb02910.x
更新日期：1986-02-01 00:00:00
abstract：:The type II histamine receptor antagonists, cimetidine and ranitidine, widely used in treatment of peptic ulcer disease have been reported to cause bradycardia. To evaluate the cardiovascular effects of H2 antagonists nineteen healthy volunteers were entered into a double-blind crossover comparison of cimetidine 300 m...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/j.1552-4604.1989.tb03365.x
更新日期：1989-05-01 00:00:00
abstract：:Lofexidine, an antihypertensive imidazoline derivative, was given to ten hypertensives on both a twice-daily and once-daily regimen, using routine blood pressure measurements and 24-hour Remler recording. Plasma renin activity and catecholamines were measured. After a dose titration with twice-daily doses, the total t...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1981.tb05697.x
更新日期：1981-04-01 00:00:00
abstract：:Nintedanib, a triple angiokinase inhibitor, has undergone clinical investigation for the treatment of solid tumors and idiopathic pulmonary fibrosis. Nintedanib (Vargatef® ) plus docetaxel is approved in the EU for the treatment of patients with adenocarcinoma non-small cell lung cancer (NSCLC) after first-line chemot...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/jcph.752
更新日期：2016-11-01 00:00:00
abstract：:Pharmacokinetics (PK) of doripenem was determined during high volume hemodiafiltration (HVHDF) in patients with septic shock. A single 500 mg dose of doripenem was administered as a 1 hour infusion during HVHDF to 9 patients. Arterial blood samples were collected before and at 30 or 60 minute intervals over 8 hours (1...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/jcph.432
更新日期：2015-04-01 00:00:00
abstract：:A prospective study of adverse drug reactions was recently completed at the Clinical Pharmacology Unit of J. J. Group of Hospitals. 338 patients were included in this study, and adverse reactions were noted by a team of workers including a nurse and a physician. World Health Organization definitions were used to descr...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1975.tb02365.x
更新日期：1975-05-01 00:00:00
abstract：:Beverage-drug interactions have remained an active area of research and have been the subject of extensive investigations in the past 2 decades. The known mechanisms of clinically relevant beverage-drug interactions include modulation of the activity of cytochrome P450 (CYP) 3A and organic anion-transporting polypepti...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1002/jcph.563
更新日期：2015-12-01 00:00:00
abstract：:The decrease in renal blood flow (RBF) observed in patients with hypertension can be increased with converting enzyme inhibition (CEI). It is unknown whether the decrease in RBF observed with age can also be increased with CEI. This study compared the short- and long-term effects of captopril monotherapy in young (les...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1991.tb01888.x
更新日期：1991-01-01 00:00:00
abstract：:In vitro dissolution profile testing of 12 generic 6-propyl-2-thiouracil (PTU) formulations indicated significant differences in their solubilities in water and in 0.1N hydrochloric acid. Two products, representing the extremes of solubility, were subsequently tested for bioavailability. Bioavailability data from euth...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1980.tb02530.x
更新日期：1980-02-01 00:00:00
abstract：:Continuous Holter recordings are often used in thorough QT studies (TQTS), with multiple 10-second electrocardiograms (ECGs) visually selected around predesignated time points. The authors hypothesized that computer-automated ECG selection would reduce within-subject variability, improve study data precision, and incr...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1177/0091270011430505
更新日期：2012-12-01 00:00:00
abstract：:We administered 0.5-and 1.0-mg doses of bumetanide intravenously to eight normal subjects with and without pretreatment with probenecid. Probenecid did not effect either the cumulative response or the time course of response of bumetanide. These results are in contrast to results reported in dogs but consistent with s...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1981.tb01772.x
更新日期：1981-07-01 00:00:00
abstract：:This study outlines the attempts of four states (Louisiana, Kansas, Wisconsin, and Michigan) to restrict anorectic prescriptions. The actions in these four states exemplify the various mechanisms used in regulating anorectics, ranging from educational efforts to legislative enactments. We examine the evidence used in ...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：
更新日期：1988-05-01 00:00:00
abstract：: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 faste...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1002/jcph.391
更新日期：2015-02-01 00:00:00
abstract：:The disposition of nalmefene, an opioid antagonist intended for the reversal of opioid-induced respiratory depression, and its primary metabolite nalmefene glucuronide, were characterized in adult volunteers with normal renal function and in patients with end-stage renal disease (ESRD). The effect of hemodialysis on t...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1996.tb04179.x
更新日期：1996-02-01 00:00:00
abstract：:Using a sensitive and specific radioimmunoassay the pharmacokinetic disposition of clonidine was determined in hypertensive patients after a single dose and then after 5, 28 and 56 days of chronic dosing with 75 micrograms bd. Following a single dose of clonidine maximal plasma concentrations of 0.34 +/- 0.06 ng/ml we...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1989.tb03335.x
更新日期：1989-04-01 00:00:00
