Abstract：
:Categorizations of best response observed at week 8 (between week 3 and 14) of first-line treatment in two studies of bevacizumab plus chemotherapy in Western (878 patients) and Chinese (198 patients) patients with non-small cell lung cancer were assessed together with baseline prognostic factors in multivariate parametric models to predict overall survival (OS) and progression free survival (PFS). Predictive performances of the models were assessed by simulating multiple replicates of the studies. Disease control rate (DCR) was the best response categorization to predict OS and PFS. In the OS model, DCR fully captured bevacizumab effect. For PFS, DCR did not fully capture bevacizumab treatment effect. The models adequately predicted OS and PFS distributions in each arm as well as bevacizumab hazard ratio (HR) for OS and PFS, for example, in Western patients (model prediction [95% prediction interval]: 0.84 [0.71-0.98] vs. observed: 0.77 for OS and 0.59 [0.49-0.72] vs. observed: 0.58 for PFS). Covariates in the models captured endpoint differences seen in Chinese patients. There was no impact of Chinese ethnicity on the DCR relationship to OS or PFS. DCR predicted OS benefit with bevacizumab in first-line NSCLC patients. Western data can be used to inform design of studies in Chinese patients.
journal_name
J Clin Pharmacoljournal_title
Journal of clinical pharmacologyauthors
Claret L,Gupta M,Han K,Joshi A,Sarapa N,He J,Powell B,Bruno Rdoi
10.1002/jcph.191subject
Has Abstractpub_date
2014-03-01 00:00:00pages
253-7issue
3eissn
0091-2700issn
1552-4604journal_volume
54pub_type
杂志文章,随机对照试验abstract：:Dual inhibition of neutral endopeptidase 24.11 (NEP) and angiotensin-converting enzyme (ACE) has gained increasing interest in the treatment of hypertension, heart failure, and renoprotection. Specifically, M100240, the thioester of the dual ACE/NEP inhibitor MDL100,173, has been evaluated in the management of hyperte...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1177/0091270004265365
更新日期：2004-06-01 00:00:00
abstract：:The safety, tolerability, and pharmacokinetics of orally administered enzastaurin were evaluated in 2 placebo-controlled, dose escalation studies in healthy subjects. In the first human dose study, single doses (2-400 mg) were evaluated, with 22 subjects receiving enzastaurin. The mean half-lives of enzastaurin and it...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1177/0091270007304775
更新日期：2007-09-01 00:00:00
abstract：:To explore the clinical relevance of inhibition of multidrug resistance transporter 1 and organic anion transporting polypeptide transporter, a drug-drug interaction study was conducted using aliskiren and cyclosporine. This was an open-label, single-sequence, parallel-group, single-dose study in healthy subjects. Sub...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1177/0091270010385934
更新日期：2011-11-01 00:00:00
abstract：:Buprenorphine administered sublingually is a promising treatment for opiate dependence. Utilizing a new, sensitive, and specific gas chromatographic electron-capture detector assay, the absolute bioavailability of sublingual buprenorphine was determined in six healthy volunteers by comparing plasma concentrations afte...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1177/009127009703700106
更新日期：1997-01-01 00:00:00
abstract：:The primary albumin binding site of indomethacin is remote from the bilirubin binding site. Indomethacin is, at most, a weak displacer of bilirubin at low serum drug concentrations. When administered at dosages less than 1 mg/kg, indomethacin would appear to be safe with respect to serum binding of bilirubin in premat...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1978.tb01575.x
更新日期：1978-10-01 00:00:00
abstract：:The increased availability of chemical intermediates and automated instrumentation has resulted in expanded use of stable isotopes for bioavailability and bioequivalence studies in recent years. Initially, stable isotopes were confined to the labeling of mass internal standard compounds for gas chromatography/mass spe...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1986.tb03551.x
更新日期：1986-07-01 00:00:00
abstract：:Sixteen healthy volunteers were given either oral or intravenous doses of aminophylline (125 mg) at 9:00 A.M. and 9:00 P.M. under controlled food conditions. Measured at regular time intervals by homogeneous enzyme immunoassay, the plasma theophylline concentrations 1.5 and 2 hours after oral aminophylline were signif...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1984.tb02760.x
更新日期：1984-11-01 00:00:00
abstract：:Consumption of typical quantities of grapefruit juice (GFJ) increases the oral bioavailability of several CYP3A4 substrates without affecting their elimination, consistent with selective inhibition of intestinal but not hepatic CYP3A4. However, increases in the AUCs of CYP3A4 substrates recently associated with the co...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1177/0091270003256059
更新日期：2003-08-01 00:00:00
abstract：:This analysis was conducted to characterize the pharmacokinetics and pharmacodynamics of pegfilgrastim and to develop a pharmacokinetic-pharmacodynamic model to describe the granulopoietic effects of pegfilgrastim and the homeostatic regulation of pegfilgrastim clearance in healthy subjects. Pegfilgrastim serum concen...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1177/0091270006288731
更新日期：2006-07-01 00:00:00
abstract：:The most commonly used Parkinson's disease (PD) treatment is the replacement of dopamine by its levodopa precursor (l-dopa). Monoamine oxidase-B (MAO-B) and catechol-o-methyl transferase (COMT) are enzymes involved in the metabolism and regulation of dopamine availability. In our study we investigated the possible rel...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.1096
更新日期：2018-07-01 00:00:00
abstract：:Limited data characterize pharmacokinetic interactions between cephalexin and ranitidine, and no data exist for an interaction with proton pump inhibitors. The purpose of this study was to investigate the effects of ranitidine or omeprazole administration on the pharmacokinetics and pharmacodynamics of cephalexin. A r...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1177/0091270004269558
更新日期：2004-12-01 00:00:00
abstract：:Advances in microcomputer technology provide new ways of incorporating PBL procedures in clinical pharmacology courses. Developments in graphics-user interfaces and analog/digital systems that display physiologic information directly on the monitor enable the computer to serve as a learning resource as laboratory clas...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1991.tb04962.x
更新日期：1991-03-01 00:00:00
abstract：:This study was undertaken to determine whether rofecoxib can interfere with CYP1A2 activity in humans using theophylline as a probe substrate. Single oral doses of theophylline were administered to each of three panels of 12 healthy subjects receiving daily doses of rofecoxib for 7 days to examine the effect of rofeco...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1177/0091270003257454
更新日期：2003-10-01 00:00:00
abstract：:The effects of long-term triple drug therapy on renal function in patients with moderate to severe essential hypertension have not been evaluated systematically. We prospectively studied fifteen male patients with moderate to severe essential hypertension receiving triple drug therapy (metolazone, atenolol or betaxolo...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1989.tb03423.x
更新日期：1989-09-01 00:00:00
abstract：:Many drugs have incomplete systemic availability after oral dosage. This can be attributed to incomplete absorption from the gastrointestinal tract, or to presystemic extraction, in which a fraction of an orally administered dose is biotransformed before reaching the systemic circulation. Presystemic extraction can oc...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1993.tb04719.x
更新日期：1993-07-01 00:00:00
abstract：:The need for clinical pharmacology in research and education, drug development, and health care delivery is well known. However, a current profile of those working in the field is not available. The ACCP authorized a survey of clinical pharmacologists to provide such a profile. Members of the ACCP or ASCPT were solici...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1989.tb03404.x
更新日期：1989-08-01 00:00:00
abstract：:There is an increasing interest in the simultaneous administration of several probe substrates to characterize the activity of multiple drug-metabolizing enzymes, the so-called "cocktail" approach. However, this method remains controversial and is being investigated more extensively. No general consensus has emerged o...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1177/0091270003261333
更新日期：2004-02-01 00:00:00
abstract：:This was a preliminary feasibility study to assess the pharmacokinetics and acute safety of a single dose of orally inhaled testosterone via the AERx system, a novel handheld aerosol delivery system in postmenopausal women. Twelve postmenopausal women stabilized on oral estrogen therapy were treated with a single dose...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1177/0091270004269840
更新日期：2005-02-01 00:00:00
abstract：:Compared with aminoglycosides, chloramphenicol, sulfonamides, tetracyclines, and even penicillins, the cephalosporins represent a remarkably safe class of antibiotics. Among the cephalosporins, the extended spectrum, third generation agents developed generally produce few side effects and appear to be less allergenic ...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1002/j.1552-4604.1990.tb03476.x
更新日期：1990-05-01 00:00:00
abstract：:The objectives of the 3 phase I studies described herein were (1) to compare the pharmacokinetics of gabapentin delivered from a novel gastric-retentive dosage form vs an immediate-release formulation, (2) to assess the dose proportionality of the gastric-retentive extended-release formulation, and (3) to determine th...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1177/0091270010368411
更新日期：2011-03-01 00:00:00
abstract：:More than 30% of patients who undergo surgery will experience postoperative nausea and vomiting (PONV) if no prophylactic treatments are used. Although numerous studies have been performed to investigate the factors related to PONV, the effect of perioperative intravenous oxycodone on the incidence of PONV has not bee...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1002/jcph.1408
更新日期：2019-08-01 00:00:00
abstract：:Acebutolol, a beta-1 selective beta blocker with intrinsic sympathomimetic activity has been shown to be an effective agent in chronic angina pectoris therapy, with twice or three times daily dosing. The long-term effects of 400 mg of acebutolol given only once a day versus placebo on exercise hemodynamics, ST segment...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/j.1552-4604.1988.tb05754.x
更新日期：1988-05-01 00:00:00
abstract：:Dienogest offers pharmacological advantages for the effective treatment of endometriosis and for use in contraception and hormone replacement therapy. This pharmacodynamic study investigated the ovulation-inhibiting effects of dienogest monotherapy in healthy women. Dienogest was administered at 0.5, 1, 2, or 3 mg dai...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1177/0091270011423664
更新日期：2012-11-01 00:00:00
abstract：:DS-1040, a low-molecular-weight imidazole derivative, inhibits the enzymatic activity of thrombin-activatable fibrinolysis inhibitor (TAFIa), enhancing endogenous tissue plasminogen activator-triggered fibrinolysis. This first-in-human, randomized, placebo-controlled, phase 1 study evaluated the safety, pharmacokineti...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1002/jcph.1474
更新日期：2019-12-01 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：:ABT-761 is a second-generation 5-lipoxygenase inhibitor in clinical development for the treatment of asthma. The effects of ABT-761 on the pharmacokinetics of an oral contraceptive were assessed in 21 female adult volunteers in a phase I, multiple-dose, open-label study. Subjects received a single dose of oral contrac...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/j.1552-4604.1998.tb04472.x
更新日期：1998-07-01 00:00:00
abstract：:Amiodarone is a unique antiarrhythmic agent originally developed as a vasodilator. Classified electrophysiologically as a Type III antiarrhythmic, it also has both nonspecific antisympathetic and direct, fast channel-membrane effects. Hemodynamic effects of orally administered amiodarone (a negative inotropic agent) a...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1002/j.1552-4604.1991.tb03673.x
更新日期：1991-11-01 00:00:00
abstract：:Isosorbide dinitrate is one of the most commonly prescribed medications for the treatment of ischemic heart disease. It has been demonstrated to be ineffective relative to placebo when taken inappropriately. This study objectively documents the magnitude and nature of compliance in 68 ambulatory patients who were pres...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1996.tb04222.x
更新日期：1996-07-01 00:00:00
abstract：:The present study was carried out to clarify the effects of an antianxiety drug and of personality characteristics on a psychomotor performance test. Forty-eight healthy women college students were chosen from 64 volunteers as having either high or low levels of trait anxiety, neuroticism, or extroversion. Subjects wi...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1978.tb02432.x
更新日期：1978-02-01 00:00:00
abstract：:The effect of telbivudine on cardiac repolarization was evaluated in healthy participants at clinical and supratherapeutic doses. Sixty-two participants were enrolled, stratified by sex, and randomized according to a crossover design among 4 treatment sequences: placebo, a single moxifloxacin 400-mg dose as positive c...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1177/0091270009337943
更新日期：2009-12-01 00:00:00
