Abstract：
AIM:The investigations reported here aimed to evaluate the incremental benefit for dose finding by concentration-response analysis versus dose-response analysis. METHODS:Trials were simulated using an Emax model for a range of scenarios of drug properties, trial design options and target response levels. The simulated data were analysed by concentration-response and dose-response modelling; a dose was then chosen to target a specific response level in a confirmatory trial. The two approaches were compared in terms of the quality of model parameter estimation and the success rate for the confirmatory trial. RESULTS:While the accuracy for ED50 estimation was comparably good with both approaches, the precision was up to 90 % higher with concentration-response approach. The difference was most notable when clearance was highly variable between subjects and the top dose was relatively low. The higher precision by the concentration-response analysis lead to better dose selection and up to 20 % higher success rate for the subsequent confirmatory trial. The relatively small difference in success rate translated into a remarkable difference in sample size requirement. CONCLUSION:By customising these parameters, the approach and the findings can be applied to assessing the value of pharmacokinetic sampling in particular trial situations.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Berges A,Chen Cdoi
10.1007/s00228-013-1474-zsubject
Has Abstractpub_date
2013-07-01 00:00:00pages
1391-9issue
7eissn
0031-6970issn
1432-1041journal_volume
69pub_type
杂志文章abstract：PURPOSE:Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor (ARNI) indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA class II-IV) and reduced ejection fraction. This study was aimed to evaluate ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1007/s00228-016-2062-9
更新日期：2016-08-01 00:00:00
abstract：:We have shown that apparent nonlinearities in the pharmacokinetics of chloroquine and wide variability in reported kinetic values are possibly artefacts of experimental design. We have used simulated data based on linear equations to demonstrate that chloroquine kinetics may appear to be dose-dependent if samples are ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00541305
更新日期：1987-01-01 00:00:00
abstract：PURPOSE:Lithium (Li), the first-line treatment of bipolar disorder, was first developed as an immediate-release form with a routine therapeutic drug monitoring 12 h after the last dose. In Europe, the most commonly prescribed form is a sustained release (srLi). Yet no pharmacokinetics (PK) study has been published of s...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-018-2605-3
更新日期：2019-04-01 00:00:00
abstract：:The incidence of vasodilation-related events (flushing, headache, dizziness and oedema) was determined in a total of 37,670 patients treated with diltiazem, nicardipine, isradipine or amlodipine and studied by Prescription-Event Monitoring between 1984 and 1991. Event rates are expressed as the percentage of patients ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00202163
更新日期：1995-01-01 00:00:00
abstract：:In a double-blind, placebo-controlled study nasal saline and histamine provocation tests were performed in patients with perennial allergic rhinitis in order to assess changes in eosinophil influx and non-specific nasal reactivity after 8 days of treatment with ipratropium bromide. A "nasal pool" method was used to tr...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/BF02440856
更新日期：1993-01-01 00:00:00
abstract：:The purpose of this study was to examine the influence of cigarette smoking and gender on the pharmacokinetics of metoprolol. Eighteen volunteers with no evidence of clinical disease each randomly received the following doses of metoprolol tartrate: 100 mg orally, 200 mg orally and 20 mg as a constant-rate intravenous...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/BF00637630
更新日期：1987-01-01 00:00:00
abstract：:In 10 healthy male subjects the pharmacokinetics and haemodynamic effects of sustained-release isosorbide-5-mononitrate 60 mg (IS-5-MN) were studied after oral administration at two different times in the day (08.00 h and 20.00 h). Effects on blood pressure and heart rate after 3 min standing upright were measured in ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00315142
更新日期：1991-01-01 00:00:00
abstract：PURPOSE:Network meta-analysis (NMA) is a new technique that allows multiple treatment comparisons and provides estimates of effect sizes for all possible pair-wise comparisons. Several NMAs of antiepileptic drug (AED) efficacy and tolerability in individuals with refractory focal epilepsy, however, came to non-specific...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,meta分析
doi：10.1007/s00228-014-1669-y
更新日期：2014-06-01 00:00:00
abstract：:Unstable angina is a clinical syndrome characterized by increased rate and severity of angina pectoris attacks and, sometimes but not always, accompanied by ECG changes similar to those seen in coronary insufficiency. According to the present conception of the pathogenesis, ruptures at points of high-grade stenosis in...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1007/BF01417569
更新日期：1990-01-01 00:00:00
abstract：:Previous studies showed that probucol significantly lowered both LDL cholesterol and HDL cholesterol. In addition, there is evidence that as an essential antioxidant probucol causes variations in cellular interactions and cardiovascular functions in patients. Therefore, 14 hypercholesterolemic men were investigated be...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-01-01 00:00:00
abstract：:In a double-blind cross-over study bepridil 900 mg followed by 300 mg daily for 11 days was given to 37 insulin (Type I) or non-insulin (Type II)-dependent diabetic patients. It did not modify the metabolic control of the patients as levels of glucose in blood and urine, doses of insulin and oral hypoglycaemic drugs, ...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/BF00540947
更新日期：1988-01-01 00:00:00
abstract：:In Belgium, all dispensed drugs are provided with package inserts. Traditional physician-orientated inserts are gradually being replaced by patient package inserts (PPIs). The present survey is focused on the use of inserts for antihypertensive drugs and their impact on the reported occurrence and attribution of adver...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00316093
更新日期：1990-01-01 00:00:00
abstract：:Serotonin (5-HT) stimulates prolactin release. In the present study the ability of dexfenfluramine to increase serum prolactin was used as an index of central 5-HT function after acute and chronic pretreatment of volunteers with fluoxetine. Following a single-blind, random design, on each experimental day each volunte...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/BF00191908
更新日期：1994-01-01 00:00:00
abstract：PURPOSE:The population pharmacokinetics (PK) of lopinavir in tuberculosis (TB)/human immunodeficiency virus (HIV) co-infected South African children taking super-boosted lopinavir (lopinavir/ritonavir ratio 1:1) as part of antiretroviral treatment in the presence of rifampicin were compared with the population PK of lo...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-010-0847-9
更新日期：2010-10-01 00:00:00
abstract：:In a model of mental stress the influence of nifedipine and hydrochlorothiazide on stress-induced changes in blood pressure, heart rate, and plasma catecholamines was studied in normal persons. The drugs were used to investigate whether substances with antihypertensive but no particular sympatholytic properties were c...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00544008
更新日期：1983-01-01 00:00:00
abstract：:Pharmacokinetic parameters of prazosin (t1/2, tmax, Cmax and AUC have been studied in 18 hypertensive patients with varying degrees of chronic renal failure (serum creatinine ranging from 1.6 to 11.4 mg/dl). An oral dose of 2 mg of prazosin was added to the preexisting antihypertensive medication. The degree of renal ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00981133
更新日期：1986-01-01 00:00:00
abstract：:The pharmacokinetics, hypotensive effect and tolerability of a new vasodilator, tolmesoxide (T), have been studied in 6 uncontrolled hypertensive patients receiving atenolol and diuretic. After a 50 mg oral dose mean (+/- SD) peak plasma concentration of T was 1.13 +/- 0.29 micrograms/ml-1 and occurred 0.79 +/- 0.40 h...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00568397
更新日期：1981-01-01 00:00:00
abstract：:The binding of propranolol, a drug commonly used in cardiovascular disorders, to alpha 1-acid glycoprotein (AGP) was studied in vitro in malnutrition. Compared to normal and hospital controls, the level of AGP was found to be elevated in undernourished subjects with and without infection. In the same patients the free...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00547044
更新日期：1985-01-01 00:00:00
abstract：PURPOSE:Drug-related problems (DRPs) are common in paediatric pharmacotherapy, but few studies describe them from the parents' perspective. In the present survey, we have investigated the lifetime prevalence and type of DRPs in children in Finland. METHODS:This was a population-based survey of a random sample of 6,000...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1007/s00228-012-1426-z
更新日期：2013-04-01 00:00:00
abstract：:The metabolic fate and ACTH-suppressant activity of two injectable dexamethasone esters, 21-phosphate and 21-sulphate, were studied in healthy men. After i.v. injection of 20mg free steroid alcohol, dexamethasone phosphate was efficiently hydrolyzed to free dexamethasone, reaching its peak plasma concentration within ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00618778
更新日期：1981-01-01 00:00:00
abstract：:We have evaluated the pharmacokinetics of high doses of clonidine, as used in the prophylactic treatment of alcohol withdrawal syndrome, in 11 alcohol-dependent patients undergoing surgery for oesophagogastrectomy. Clonidine was given in a bolus of 150 micrograms followed by a continuous infusion. After a mean period ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00315500
更新日期：1993-01-01 00:00:00
abstract：OBJECTIVE:To investigate the potential for pharmacokinetic interactions between moexipril, a new converting enzyme inhibitor, and hydrochlorothiazide after single dose administration. METHODS:12 healthy male volunteers were studied by an open, randomised, three-way cross-over design, in which single doses of moexipril...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/s002280050209
更新日期：1996-01-01 00:00:00
abstract：BACKGROUND AND OBJECTIVES:Dosing of vancomycin in pediatric patients undergoing continuous venous-venous hemodiafiltration (CVVHDF) is challenging. Characterization of vancomycin pharmacokinetics can assist with dosing and attainment of goal serum concentrations. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS:Patient...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-019-02664-7
更新日期：2019-08-01 00:00:00
abstract：OBJECTIVE:The aim of the study was to determine the changes in consumption of psychotropic drugs by children aged less than 18 years during the years 1995 to 2001 in the Netherlands. METHODS:The year prevalence of antipsychotics, benzodiazepines, antidepressants and psychostimulants for boys and girls under 18 years w...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-004-0765-9
更新日期：2004-07-01 00:00:00
abstract：BACKGROUND AND OBJECTIVES:Laryngoscopy and tracheal intubation are associated with hemodynamic responses that might increase morbidity and mortality in some patients. Lornoxicam is a nonsteroidal anti-inflammatory drug, which, when added to fentanyl, successfully attenuated the pressor response of intubation. The aim o...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1007/s00228-011-1017-4
更新日期：2011-08-01 00:00:00
abstract：:The pharmacokinetics of lorazepam was examined in 10 male patients with insulin-dependent diabetes mellitus before and following treatment with neomycin and cholestyramine. Neomycin and cholestyramine were given in an attempt to block the enterohepatic circulation of lorazepam and so to permit an in vivo estimate of h...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00198307
更新日期：1995-01-01 00:00:00
abstract：OBJECTIVE:To investigate the CYP1A2 phenotype distribution in a population with an increased exposure to polychlorinated biphenyls (PCBs) that would likely induce an increased activity of this enzyme. Further, to investigate the effect of sex, smoking, and oral contraceptive use on the CYP1A2 activity. METHODS:In 305 ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-006-0205-0
更新日期：2006-12-01 00:00:00
abstract：BACKGROUND:Cytochrome P450 2C9 (CYP2C9) allelic variant carriers have been shown to experience hyper-responsiveness to small doses of oral anticoagulants (OAs) (warfarin or acenocoumarol) and a higher bleeding rate. OBJECTIVES:To determine the relative frequencies of different risk factors for OA overdose including di...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-002-0538-2
更新日期：2003-03-01 00:00:00
abstract：OBJECTIVES:Problem-oriented drug information is characterised by health professionals actively seeking drug information through various sources. In this study our objective was to determine the quality and impact of problem-oriented drug information among physicians. METHODS:Evaluation forms accompanying 163 written a...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-001-0386-5
更新日期：2002-02-01 00:00:00
abstract：PURPOSE:As an inhibitor of HMG-CoA reductase that catalyses the first step of cholesterol synthesis, pitavastatin undergoes little hepatic metabolism; however, it is a substrate of uptake and efflux transporters. Since pitavastatin is potentially co-administered with agents that affect transporter activities, the pharm...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1007/s00228-013-1554-0
更新日期：2013-11-01 00:00:00
