Abstract:
:This paper reviews state-of-art statistical designs for dose-escalation procedures in first-into-man studies. The main focus will be on studies in oncology, as most statistical procedures for phase I trials have been proposed in this context. Extensions to situations such as the observation of bivariate outcomes and healthy volunteer studies are also discussed. The number of dose levels and cohort sizes used in early phase trials are considered. Finally, this paper raises some practical issues for dose-escalation procedures.
journal_name
Fundam Clin Pharmacoljournal_title
Fundamental & clinical pharmacologyauthors
Zhou Ydoi
10.1111/j.1472-8206.2004.00226.xsubject
Has Abstractpub_date
2004-06-01 00:00:00pages
373-8issue
3eissn
0767-3981issn
1472-8206pii
FCP226journal_volume
18pub_type
杂志文章,评审abstract::Fluoxetine is one of the most commonly used antidepressants. Fluoxetine could prevent the mesenchymal stem cell differentiation in lung fetus of rat. Moreover, the mesenchymal stem cells are also present in adult tissues. Therefore, in the current study, we aimed to investigate the effects of fluoxetine (FLX) on both ...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/fcp.12426
更新日期:2019-06-01 00:00:00
abstract::Strong sero-epidemiologic, pathologic, and experimental evidence suggests that Chlamydophila pneumoniae (Cpn) infection may play a causative role in the development of atherosclerosis. Cpn is an obligate intracellular gram-negative bacterium that is responsible for 10% of cases of community-acquired pneumonia. In addi...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1472-8206.2010.00863.x
更新日期:2010-10-01 00:00:00
abstract::In epileptic patients cyproheptadine is frequently prescribed as an appetite stimulant for the treatment of anorexia associated with anti-epileptic drugs and for the management of 'serotonin syndrome' in depressed epileptic patients. However, the study of serotonergic and histaminergic pathway shows that the decreased...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1472-8206.2009.00797.x
更新日期:2010-08-01 00:00:00
abstract::The formation of dopamine, from L-3,4-dihydroxyphenylalanine (L-dopa), in fragments of non-glandular and glandular stomach, duodenum, jejunum, ileum and proximal and distal colon of the rat was examined. The deamination of newly-formed dopamine into 3,4-dihydroxyphenylacetic acid (dopac) was also studied. The synthesi...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1472-8206.1993.tb00237.x
更新日期:1993-01-01 00:00:00
abstract::Prostaglandin E synthase (PGES) is a recently identified terminal enzyme that acts downstream of cyclooxygenase and catalyzes the conversion of prostaglandin (PG) H2 to PGE2. At least three isozymes have been cloned so far, which are called membrane-associated PGES (mPGES)-1, mPGES-2, and cytosolic PGES. Among them, m...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1472-8206.2005.00316.x
更新日期:2005-06-01 00:00:00
abstract::Cicletanine, a racemic furopyridine derivative synthesized as racemate, is used as an antihypertensive agent. Its two enantiomers are involved in the pharmacological effects of the drug. Cicletanine is metabolized by conjugation enzyme systems (phase II) into sulfoconjugated or glucuroconjugated enantiomers. As oxazep...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1472-8206.1999.tb00363.x
更新日期:1999-01-01 00:00:00
abstract::Gait disorders form one component of the axial disorders observed in Parkinson's disease (PD). Indeed, short steps with a forward-leaning stance are diagnostic criteria for PD in the early stages of the condition. Gait disorders also represent a major source of therapeutic failure in the advanced stages of PD (with th...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1472-8206.2009.00798.x
更新日期:2010-08-01 00:00:00
abstract::Cyclosporine A (CsA) is an immunosuppressor, which is most frequently used in the transplant surgery and in the treatment of autoimmune diseases. It has been shown that CsA is able to generate reactive oxygen species and lipid peroxidation, which are directly involved in the CsA nephrotoxicity, hepatotoxicity and card...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1472-8206.2008.00609.x
更新日期:2008-08-01 00:00:00
abstract::There is now substantial data in the literature showing that statins can protect against cerebral ischemia. This neuroprotective potency is related to their pleiotropic effects that modulate various pathways implicated in the pathophysiology of stroke. It has been demonstrated that statins exert anti-inflammatory and ...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/fcp.12035
更新日期:2014-06-01 00:00:00
abstract::A survey was run on a sample of 134 French GPs from the Rhône-Alpes region, in an attempt to investigate the way they recollect important clinical trials that should have an impact on their practice. It was found that 1) most of them did not remember these trials (however, the awareness score did vary throughout the t...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1472-8206.1991.tb00721.x
更新日期:1991-01-01 00:00:00
abstract::The prevalence of end stage renal disease (ESRD) is growing in western countries. Patients with ESRD are more frequently elderly and diabetic and are exposed to very high cardiovascular morbidity and mortality. The main aim of the FOSIDIAL study is to assess the efficacy and safety of fosinopril, an angiotensin conver...
journal_title:Fundamental & clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1046/j.1472-8206.2002.00127.x
更新日期:2002-10-01 00:00:00
abstract::This study investigated whether ivabradine, a selective If current inhibitor reducing heart rate (HR), is able to improve survival and prevent left ventricular (LV) remodeling in isoproterenol-induced heart damage. Wistar rats were treated for 6 weeks: controls (n = 10), ivabradine (10 mg/kg/day orally; n = 10), isopr...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/fcp.12620
更新日期:2020-10-24 00:00:00
abstract::The aim of this study was to investigate biochemical and antioxidant parameters in alloxan-resistant (ALR) and alloxan-susceptible (ALS) rats. Diabetes was induced in 60-day-old male Wistar rats by a single intraperitonial injection of alloxan (AL, 150 mg/kg). Ten days after induction, a group of rats showed a signifi...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1472-8206.2008.00628.x
更新日期:2008-12-01 00:00:00
abstract::We have studied the effects of neurotensin (NT) on the release of [3H]dopamine ([3H]DA) evoked by terminal depolarization with either K+, veratridine or 4-aminopyridine (4-AP). NT (1-1000 nM) induced a net potentiation (up to 170%) of the K+ (25 mM)-evoked release of [3H]DA. The capacity of NT to potentiate the effect...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1472-8206.1993.tb00224.x
更新日期:1993-01-01 00:00:00
abstract::Erythromycin inhibits the production of tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL6) induced by heat-killed Streptococcus pneumoniae in human whole blood ex-vivo. The objective of the present study was to determine and characterize the concentration-effect relationship of this phenomenon in order t...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.1472-8206.2001.00054.x
更新日期:2001-12-01 00:00:00
abstract::The effects of the dopamine receptor agonist, apomorphine, on the total catecholamine content of the adrenal medulla were studied in normotensive rats. Apomorphine (3, 15, 30 mg/kg SC) induced a dose-dependent decrease in catecholamine content of the adrenal gland. The action of apomorphine was suppressed by previous ...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1472-8206.1989.tb00467.x
更新日期:1989-01-01 00:00:00
abstract::The present study was designed to test whether tramadol is effective in the control of neuropathic pain in rats. Chronic constriction injury (CCI) of the sciatic nerve was induced over the left hind limb in male Sprague-Dawley rats. Identical surgery was performed on the opposite side except that the sciatic nerve was...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1472-8206.2000.tb00414.x
更新日期:2000-07-01 00:00:00
abstract::This study sought to identify the effect of drug reimbursability--a decision made in France by the National Authority for Health--on physicians' prescribing practices for a diet drug such as rimonabant, approved for obese or overweight patients with type-2 diabetes. A cross-sectional survey of French general practitio...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/j.1472-8206.2009.00779.x
更新日期:2010-08-01 00:00:00
abstract::A new quinoline containing selenium, 4-phenylselenyl-7-chloroquinoline (4-PSQ), was described and synthetized by our research group. Recently, we demonstrated the potential antinociceptive and anti-inflammatory of 4-PSQ. For this reason, the first objective of this study was to expand our previous findings by investig...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/fcp.12295
更新日期:2017-10-01 00:00:00
abstract::Trigeminal stimulation of C-fibers increased c-fos expression within the trigeminal nucleus caudalis (NtV) and thalamic neuronal activity which both reflect the transmission of a nociceptive message. We examined the effects on both these phenomena of the selective NK1 and NK2 receptor antagonists, SR140333 and SR48968...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1472-8206.1998.tb00929.x
更新日期:1998-01-01 00:00:00
abstract::The effects of tramadol versus placebo administration on behavioral indicators of ureteral pain, pelvic pain and referred lumbar muscle hyperalgesia were investigated in a rat model of viscero-visceral hyperalgesia from endometriosis plus ureteral calculosis (endo + stone). Fifty female Sprague-Dawley rats underwent s...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/fcp.12038
更新日期:2014-06-01 00:00:00
abstract::We estimated the effect of atorvastatin and fluvastatin on plasma antioxidative activity used in coronary heart disease (CHD) primary prevention. Anti-oxidative activity of blood plasma was determined by Bartosz et al. method [Curr. Top. Biophys. (1998)22:11-13], based on reduction of preformed cation radical of 2,2,a...
journal_title:Fundamental & clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1046/j.0767-3981.2003.00208.x
更新日期:2004-02-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to investigate the effects of intracoronary bradykinin (BK) infusion on noradrenaline release and ventricular arrhythmias induced by coronary occlusion and reperfusion in the anesthetized dog. METHODS:14 anesthetized adult mongrel dogs of either sex underwent a 60 min occlusion of t...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1472-8206.1994.tb00834.x
更新日期:1994-01-01 00:00:00
abstract::Thalidomide, a well-known immunomodulatory compound, has an anti-angiogenic activity, which may be utilized for the treatment of angiogenesis-related diseases such as hemangioendothelioma. The aim of the present study was to investigate both the antitumor role of thalidomide on hemangioendothelioma and the underlying ...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/fcp.12478
更新日期:2019-12-01 00:00:00
abstract::Chloroquine (CQ) induces histamine-independent itch in human and mice. We recently reported the role of intradermal nitric oxide (NO)/cyclic guanosine monophosphate pathway in CQ-evoked scratching in mice. Chloroquine stimulates neuronal nitric oxide synthase (nNOS) activity to over-producing NO in the skin. Sumatript...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/fcp.12317
更新日期:2018-02-01 00:00:00
abstract::This study aimed to investigate the modulation of nitric oxide/reactive oxygen species in sodium nitroprusside relaxation in mice aorta. Sodium nitroprusside induced relaxation in endothelium-intact (e+) and endothelium-denuded (e-) aortas with greater potency in e+ than in e-. The nitric oxide synthase inhibitor did ...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/fcp.12103
更新日期:2015-04-01 00:00:00
abstract::Childhood digestive disorders are a common occurrence and are sometimes unexplained. Maternal medication during the development of the foetus' digestive system may contribute to the increase in childhood digestive disorders, especially with drugs acting on the cholinergic system. This study investigated the associatio...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/fcp.12428
更新日期:2019-06-01 00:00:00
abstract::The contribution of Na+, Ca2+, and various K+ currents to the shape of the cardiac action potential is outlined based on the relation between electrophysiological properties and structure of channel molecules. These currents have also been found in human ventricular myocytes, where the most prominent K+ current is a t...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1472-8206.1996.tb00582.x
更新日期:1996-01-01 00:00:00
abstract::Oxidative stress and associated complications are the major pathological concerns of diabetic cardiomyopathy (DC). We aim to elucidate the mechanisms by which high glucose (HG) induced alteration in calcium homeostasis and evaluation of the beneficial effect of two concentrations (10 and 25 μm) of ferulic acid (FA). H...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/fcp.12452
更新日期:2019-08-01 00:00:00
abstract::Suriclone is a novel cyclopyrrolone exhibiting anxiolytic activity. Twelve healthy Caucasian male volunteers participated in the study. A single dose of suriclone 0.4 mg, imipramine 75 mg, suriclone 0.4 mg + imipramine 75 mg, or placebo was given according to a 4 x 4 Latin-square design in order to assess the effect o...
journal_title:Fundamental & clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1472-8206.1994.tb00806.x
更新日期:1994-01-01 00:00:00