Abstract：
OBJECTIVE:The extrapolated area under the concentration-time curve (AUC0-infinity) for any drug is considered by operating guidelines as the primary parameter related to the extent of absorption in single-dose bioavailability and bioequivalence trials. Not more than 20% should be added to the experimental AUC (AUC0-t) in the extrapolating procedure. However, in certain specific cases, it is problematic and, in other cases, impossible to respect the above requirement. It was intended to demonstrate that truncated AUC or AUC0-t would be used in bioequivalence trials when the AUC cannot be extrapolated. METHODS:AUC0-t and truncated AUC were compared at various time intervals with AUC0-infinity in a series of 19 single-dose bioequivalence trials covering 15 different drugs, each carried out on 12-24 healthy volunteers. Point estimators and 90% confidence intervals in the 0.80-1.25 and 0.70-1.43 ranges were statistically processed using log-transformed parameters. RESULTS:In all the trials considered, overlapping point estimators and 90% confidence intervals were invariably obtained, regardless of the AUC used. CONCLUSION:The use of AUC0-t or truncated AUC may be considered an ancillary procedure in bioequivalence trials when AUC cannot be extrapolated. This occurs with most extended-release formulations, endogenous substances, and poorly absorbed drugs. It also occurs in trials with one or more poor metabolisers, with drugs possessing very long elimination half-lives, and with bioassays having problems of sensitivity that preclude sufficiently precise plasma concentration measurement over the required sampling period.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Marzo A,Monti NC,Vuksic Ddoi
10.1007/s002280050684subject
Has Abstractpub_date
1999-11-01 00:00:00pages
627-31issue
9eissn
0031-6970issn
1432-1041journal_volume
55pub_type
杂志文章abstract：OBJECTIVES:The study was conducted to investigate whether oral co-administration with citrus juices significantly affects the pharmacokinetics and/or pharmacodynamics of pranidipine, a new 1,4-dihydropyridine calcium antagonist, in healthy male subjects. Grapefruit juice and orange juice, which were both commercially a...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/s002280050547
更新日期：1998-11-01 00:00:00
abstract：BACKGROUND:Zolmitriptan is a 5HT(1B/1D) receptor agonist effective in the acute treatment of migraine. Clinical trials in the USA and Europe have demonstrated the optimal oral therapeutic dose to be 2.5 mg. The 2.5-mg oral tablet has recently been licensed in Japan. OBJECTIVE:To compare the pharmacokinetics of zolmitr...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,多中心研究
doi：10.1007/s00228-002-0461-6
更新日期：2002-07-01 00:00:00
abstract：BACKGROUND AND OBJECTIVES:Opicapone is a novel third generation catechol-O-methyltransferase (COMT) inhibitor. The purpose of this study was to compare the levodopa pharmacokinetic profile throughout a day driven by the COMT inhibition either following repeated doses of opicapone or concomitant administration with enta...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1007/s00228-014-1701-2
更新日期：2014-09-01 00:00:00
abstract：:A randomised, placebo controlled clinical trial was conducted to examine the efficacy of a homeopathic after-bite gel in the symptomatic relief of mosquito bites. Sixty eight healthy volunteers were bitten under laboratory conditions by Aedes aegypti mosquitoes at three spots, on the ventral aspect of the forearm. One...
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/BF00192367
更新日期：1995-01-01 00:00:00
abstract：:Blood levels of racemic chloroquine and its main metabolites desethylchloroquine and bisdesethylchloroquine were measured in 29 patients treated chronically for rheumatoid arthritis. In six patients, the concentrations were followed during a one day dosage interval. There was considerable intersubject variability in t...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00280130
更新日期：1992-01-01 00:00:00
abstract：OBJECTIVES:To assess relative roles of the intestinal and hepatic stereoselective metabolism of nicardipine in an oral first-pass disposal with and without grapefruit juice intake. METHODS:The kinetic profiles of (+)- and (-)-nicardipine were studied in the six normal healthy male volunteers who received oral (40 mg) ...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/s002280000235
更新日期：2000-12-01 00:00:00
abstract：PURPOSE:Oncological patients are at increasing risk of QT prolongation, a risk factor for ventricular arrhythmia. We assessed impact and risk factors for corrected QT (QTc) prolongation during multiple-cycle chemotherapy. METHODS:We enrolled 100 outpatients initiating chemotherapy in a university center specializing i...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-015-1874-3
更新日期：2015-08-01 00:00:00
abstract：PURPOSE:Bariatric surgery can influence the prevalence and incidence of comorbidities, as well as the pharmacokinetics of drugs. This might lead to changes in the use of drugs. This study aimed to assess the influence of bariatric surgery on the use of medication in patients before and after surgery, focusing on type, ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-015-1971-3
更新日期：2016-02-01 00:00:00
abstract：OBJECTIVES:To analyse reports of drug-induced myocardial infarction and chest pain sent to a national reporting centre. To review which drugs were suspected of exhibiting these adverse events and what mechanisms were involved. METHODS:During the 20-year period 1975 through 1994, a total of 19,141 reports on adverse re...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1007/s002280050346
更新日期：1997-01-01 00:00:00
abstract：AIM:Our aim was to characterize utilization patterns for drugs used to treat attention deficit/hyperactivity disorder (ADHD) on the level of the individual patient among Danish users, focusing on treatment duration, doses used, and concurrent use of ADHD and non-ADHD drugs. METHODS:Using the Danish Registry of Medicin...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-012-1344-0
更新日期：2013-03-01 00:00:00
abstract：OBJECTIVE:We investigated whether interindividual differences in the pharmacokinetic disposition of lansoprazole are attributed to the genetic polymorphism of CYP2C19 which occurred by two mutations. CYP2C19m1 and CYP2C19m2, in 20 Japanese subjects. METHODS:Polymerase chain reaction (PCR) restriction fragment length p...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s002280050307
更新日期：1997-01-01 00:00:00
abstract：:Potentiation of the anticoagulant-effect of warfarin by amiodarone was studied in 30 patients. Thirteen received both drugs concurrently, and 17 received warfarin alone and the combination sequentially. Warfarin doses were adjusted to maintain the prothrombin time between 25-30% of control and its kinetics were compar...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00543320
更新日期：1985-01-01 00:00:00
abstract：:Since little is known of the number and types of binding sites on alpha 1-acid glycoprotein (AAG) and because drug-drug protein binding interactions often fail to fit a simple model, a study of the effect of 9 known AAG binding drugs on lidocaine free fraction (LFF) was performed. Serum was obtained from 10 healthy ma...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF01037957
更新日期：1983-01-01 00:00:00
abstract：:The benzamide-derivative moclobemide (Ro 11-1163) is a new short-acting, reversible MAO-inhibitor, preferentially affecting Type A MAO, which is, being developed as an antidepressant agent. The effect of moclobemide on heart rate, blood pressure, electrocardiographic and systolic time intervals was assessed in eight h...
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/BF00543787
更新日期：1983-01-01 00:00:00
abstract：PURPOSE:Acetaminophen (APAP) protein adducts are a biomarker of APAP metabolism, reflecting oxidation of APAP and generation of the reactive metabolite N-acetyl-p-benzoquinone imine. High levels of adducts correspond to liver toxicity in patients with APAP-related acute liver failure. Adduct formation following low-dos...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/s00228-012-1410-7
更新日期：2013-04-01 00:00:00
abstract：PURPOSE:To assess, with all available trial information, whether the assessment of the PRECIS-2 nine domains could provide a clear distinction between medicine masked pragmatic randomized controlled trials (pRCTs) and open-label pRCTs. METHODS:A search was conducted of participant-level pRCTs on medicines published on...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-020-03030-8
更新日期：2020-10-26 00:00:00
abstract：:Thirty patients suffering from essential hypertension were treated successively with placebo, hydralazine alone, and pindolol (Visken) combined with hydralazine. Hydralazine caused a statistically significant reduction in blood pressure and an increase in pulse rate as compared with the placebo: palpitations were an i...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/BF00614002
更新日期：1975-12-19 00:00:00
abstract：:A single dose of 60 mg trimetazidine (the normal daily dose) improved exercise capacity in angina pectoris, as reflected by an increase in the duration of exercise, total work performed, and improvement in ECG signs of ischaemia. All these effects occurred without any detectable chronotropic or vasomotor effect. The i...
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/BF00544569
更新日期：1987-01-01 00:00:00
abstract：OBJECTIVES:To compare 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) as substrates for the methylation reaction catalysed by the enzyme thiopurine S-methyltransferase (TPMT). METHODS:TPMT activity in haemolysed red blood cells of healthy blood donors was determined twice, using the same experimental setting and equa...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s002280000137
更新日期：2000-07-01 00:00:00
abstract：:The four sulphonamides studied--furosemide, tolbutamide, sulfafurazole and sulfonamidochlorobenzoic acid--bind to human albumin at the same sites but with decreasing affinity. These sites are also common to other drugs, namely acenocoumarin, chlorophenoxyisobutyric acid, phenylbutazone and warfarin. In plasma, the fou...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00609473
更新日期：1976-06-15 00:00:00
abstract：:In healthy normal subjects following the administration of labetalol the pharmacological effects were measured and compared with the plasma concentrations achieved. The inhibition of exercise induced tachycardia and inhibition of exercise induced increases in systolic pressure were significantly related to the adminis...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00562897
更新日期：1977-01-03 00:00:00
abstract：OBJECTIVE:In order to document the stereoselective distribution in joints of a chiral nonsteroidal anti-inflammatory drug, the relative affinities of the enantiomers of tiaprofenic acid in synovium and for cartilage were compared. METHODS:The distribution of tiaprofenic acid in synovium and in cartilage was studied 25...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s002280050109
更新日期：1996-01-01 00:00:00
abstract：:The effects of sodium nitroprusside (SNP) and 3-morpholino sydnonimine (SIN-1), isosorbide dinitrate (ISDN) and glyceryl trinitrate (GTN), and molsidomine (the inactive precursur of SIN-1) on monocyte chemotaxis and cyclic GMP (cGMP) concentration were studied. SNP and SIN-1 inhibited monocyte N-formyl-methionyl-leucy...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00315350
更新日期：1993-01-01 00:00:00
abstract：OBJECTIVE:In patients with schizophrenia, risperidone and olanzapine are the two most commonly used atypical anti-psychotics. A recent meta-analysis based on randomized trials suggests that, in the long term, olanzapine can have a lower frequency of treatment discontinuation (or dropout) in comparison with risperidone....
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-003-0705-0
更新日期：2004-02-01 00:00:00
abstract：:The use of cimetidine in general practice was studied in relation to the guidelines approved by the Dutch National Drug Regulatory Agency (DRA). National and regional figures showed that the frequency with which cimetidine was prescribed in general practice was greater than could be explained on the basis of approved ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00542346
更新日期：1983-01-01 00:00:00
abstract：:Intensive monitoring of adverse drug reactions (ADR) in infants and preschool children in the paediatric outpatient unit covering the town of Karlovac (150,000 inhabitants) was performed over a period of three months. Data were obtained by physical examination of children and the history given by their parents. In all...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00561025
更新日期：1989-01-01 00:00:00
abstract：PURPOSE:The existence of a sex-by-formulation interaction in bioequivalence studies implies that the bioequivalence results (i.e., the test/reference ratio of the pharmacokinetic parameters) obtained in one sex are not similar to those obtained in the other sex. Therefore, results obtained in studies including only mal...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1007/s00228-019-02632-1
更新日期：2019-06-01 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 concentration of chlorpromazine (CPZ) in hair was measured to demonstrate its value as an index of individual dosage history and compliance. An animal study using pigmented rats was conducted to confirm the dose-dependent accumulation of CPZ in hair. The concentration of CPZ in hair, newly regrown on a denuded are...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00315540
更新日期：1993-01-01 00:00:00
abstract：PURPOSE:We investigated the role of genetic, physiological, environmental, and epigenetic factors in regulating CYP2A6 expression and nicotine metabolism. METHODS:Human livers (n = 67) were genotyped for CYP2A6 alleles and assessed for nicotine metabolism and CYP2A6 expression (mRNA and protein). In addition, a subset...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-009-0762-0
更新日期：2010-03-01 00:00:00
