Abstract：
OBJECTIVES:To evaluate zolpidem as a mechanism-based inactivator of human CYP3A in vitro, and to assess its metabolic interaction potential with CYP3A drugs (in vitro-in vivo extrapolation; IV-IVE). METHODS:A co- vs. pre-incubation strategy was used to quantify time-dependent inhibition of human liver microsomal (HLM) and recombinant CYP3A4 (rCYP3A4) by zolpidem. Experiments involving a 10-fold dilution step were employed to determine the kinetic constants of inactivation (K (I) and k (inact)) and to assess the in vitro mechanism-based inactivation (MBI) criteria. Inactivation data were entered into the Simcyp population-based ADME simulator to predict the increase in the area under the plasma concentration-time curve (AUC) for orally administered midazolam. RESULTS:Consistent with MBI, the inhibitory potency of zolpidem toward CYP3A was increased following pre-incubation. In HLMs, the concentration required for half maximal inactivation (K (I)) was 122 microM and the maximal rate of inactivation (k (inact)) was 0.094 min(-1). In comparison, K (I) and k (inact) values with rCYP3A4 were 50 microM and 0.229 min(-1), respectively. Zolpidem fulfilled all other in vitro MBI criteria, including irreversible inhibition. The mean oral AUC for midazolam in healthy volunteers was predicted to increase 1.1- to 1.7-fold due to the inhibition of metabolic clearance by zolpidem. Elderly subjects were more sensitive to the interaction, with mean increases in midazolam AUC of 1.2- and 2.2-fold for HLM IV-IVE and rCYP3A4 IV-IVE, respectively. CONCLUSIONS:Zolpidem is a relatively weak mechanism-based inactivator of human CYP3A in vitro. Zolpidem is unlikely to act as a significant perpetrator of metabolic interactions involving CYP3A.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Polasek TM,Sadagopal JS,Elliot DJ,Miners JOdoi
10.1007/s00228-009-0760-2subject
Has Abstractpub_date
2010-03-01 00:00:00pages
275-83issue
3eissn
0031-6970issn
1432-1041journal_volume
66pub_type
杂志文章abstract：:Pharmacokinetic and metabolic studies with 3H-etilefrine were performed to assess the importance of a first-pass effect on the pharmacodynamic action of this sympathomimetic amine. Identical amounts of 3H-activity, ca. 80% of the dose, were excreted in the urine after intravenous or oral administration, which indicate...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00614015
更新日期：1975-12-19 00:00:00
abstract：OBJECTIVE:Databases of subjects receiving antidepressants provide evidence on the use of drugs in typical patients and settings under real-world conditions. This study analysed a general practice database to estimate the prevalence of antidepressant drug use, describe the use of these compounds by gender and age and es...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s002280100361
更新日期：2001-10-01 00:00:00
abstract：:Milrinone, a new, nonglycosidic inotropic agent with peripheral vasodilating properties, was given as a single oral 5 mg dose to 7 healthy subjects, 7 patients with moderate renal impairment (CRI I, creatinine clearance 30-63 ml/min) and 7 patients with severe renal impairment had hypertension. The mean urinary recove...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00635891
更新日期：1986-01-01 00:00:00
abstract：:The effects of the beta-blocker atenolol on vigilance, concentration, and psychophysiological condition were determined by measuring visual reaction time and choice reaction time in volunteers subjected to combined physical and mental stress. Atenolol 50 mg or placebo were administered for three days in a double-blind...
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/BF00543710
更新日期：1985-01-01 00:00:00
abstract：:The plasma levels and myocardial content of verapamil and its metabolites norverapamil, N-dealkylverapamil and N-dealkylnorverapamil were determined in 15 patients with valvular [3] or ischaemic [12] heart disease. The mean myocardial plasma concentration ratio (M/P) was 7.05 for verapamil, 11.45 for norverapamil, 8.9...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00607910
更新日期：1985-01-01 00:00:00
abstract：:The pharmacokinetic profiles of transdermal timolol 6 and 24 mg (as 5 and 20% w/v patches) was studied in four healthy young volunteers. To assess its bioavailability, the pharmacokinetics of an IV infusion of timolol maleate 5 mg was also determined in the same subjects. When the 20% (w/v) timolol patch was applied, ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00315551
更新日期：1993-01-01 00:00:00
abstract：:A phamacokinetic study in man has been made of a new dosage form of diclofenac hydroxyethylpyrrolidine (DIEP); soluble salt packed in sachets was compared with diclofenac sodium as enteric coated tablets. Oral DIEP 2 X 50 mg showed a significant difference in absorption kinetics (ka, lag time and tmax) as compared to ...
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/BF00265987
更新日期：1990-01-01 00:00:00
abstract：:The pharmacokinetic parameters of deacetyl metipranolol were determined after i.v. infusion of increasing doses (6-25mg) in 17 normal volunteers. In a second cross-over trial, deacetyl metipranolol 10 and 20mg were infused in a further 10 subjects, and in a third trial another 20 volunteers received metipranolol 40mg ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00637616
更新日期：1982-01-01 00:00:00
abstract：:A series of elegant experimental studies and careful clinical observation over a decade or more have led to the concept of 'infarct expansion' and 'remodelling' of the heart, culminating in a number of major mortality studies indicating the effectiveness of angiotensin-converting enzyme (ACE) inhibitors in patients af...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：
更新日期：1996-01-01 00:00:00
abstract：OBJECTIVE:The aim of the present study was to investigate the pharmacokinetic profile of tramadol hydrochloride in neonates, born from mothers who underwent analgesia with tramadol for the relief of labour pain. METHODS:Intramuscular tramadol (100--250 mg) was administered to 22 mothers giving birth who requested pain...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-005-0955-0
更新日期：2005-08-01 00:00:00
abstract：:The effect of the GABAergic drug sodium valproate (SV) on the exercise-induced release of growth hormone (GH) was investigated in 10 healthy males. The exercise test consisted of using a stationary bicycle ergometer at 450 kg/min for 20 min. SV 600 mg blunted the increase in GH induced by the exercise, suggesting GABA...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00544075
更新日期：1985-01-01 00:00:00
abstract：:The inhibitory action of azelastine hydrochloride (Azeptin) on the respiratory burst in peripheral polymorphonuclear leukocytes (PMN) and pulmonary alveolar macrophages (PAM) has been studied. Azeptin in vitro suppressed chemiluminescence and superoxide (O2-) generation by human PMN in a dose- and time-dependent manne...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00194963
更新日期：1994-01-01 00:00:00
abstract：PURPOSE:Perhexiline is a prophylactic anti-ischaemic agent with weak calcium antagonist effect which has been increasingly utilised in the management of refractory angina. The metabolic clearance of perhexiline is modulated by CYP2D6 metaboliser status and stereoselectivity. The current study sought to (1) determine wh...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1007/s00228-015-1934-8
更新日期：2015-12-01 00:00:00
abstract：:The linearity of the pharmacokinetics of the metamizol metabolites 4-methyl-amino-antipyrine (4-MAA), 4-amino-antipyrine (4-AA), 4-formyl-aminoantipyrine (4-FAA), and 4-acetyl-amino-antipyrine (4-AcAA) has been studied after administration to 15 healthy male volunteers of single oral doses of 750, 1500, and 3000 mg me...
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/BF00314805
更新日期：1990-01-01 00:00:00
abstract：PURPOSE:Gefitinib is one of the standard treatments for non-small cell lung cancer (NSCLC) with epidermal growth factor receptor mutations. It has been reported that acid suppressants (AS) decrease the anti-tumor effect of gefitinib by reducing its solubility. AS is sometimes necessary in cancer patients; however, prev...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-020-03013-9
更新日期：2020-10-07 00:00:00
abstract：PURPOSE:The objective of this study was to appraise the safety profiles of HES preparations and to find out which HES preparation was the most acceptable in cardiovascular surgery through a comparison with control solutions. METHODS:Pertinent randomized controlled trials were selected through a search of Pubmed, Embas...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,meta分析,评审
doi：10.1007/s00228-011-1008-5
更新日期：2011-08-01 00:00:00
abstract：:17 patients with severe digoxin intoxication were successfully treated with 320 to 480 mg Fab fragments of digoxin-specific IgG from sheep. The infusion period ranged between 0.5 and 7 h. Serum and urine concentrations of digoxin bound to Fab fragments, and in 11 cases unbound Fab fragments in serum, were determined d...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00542410
更新日期：1986-01-01 00:00:00
abstract：:The effects of guar gum (GG) and microcrystalline cellulose (MC) on metabolic control and serum lipids were compared in a double-blind, cross-over trial in 18 poorly controlled Type 2 diabetic patients. There were two 12 week treatment periods separated by a 4 week wash-out period. A significant reduction in fasting B...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/BF00542449
更新日期：1988-01-01 00:00:00
abstract：OBJECTIVE:We sought to quantify the influence of the CYP3A inhibitor erythromycin on the pharmacokinetics of everolimus, a CYP3A substrate. METHODS:This was a two-period, single-sequence, crossover study in 16 healthy subjects. In period 1, subjects received the reference treatment of a single 2-mg dose of everolimus....
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/s00228-004-0866-5
更新日期：2005-03-01 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：OBJECTIVES:Caffeine-containing beverages are generally consumed by Nigerians suffering from malaria and kwashiorkor in the belief that caffeine aids early recovery from these illnesses, which are common in the tropics. However, there are no studies on the influence of these diseases on the absorption and pharmacokineti...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/s002280050734
更新日期：2000-05-01 00:00:00
abstract：PURPOSE:The purpose of this study is to investigate whether there is an association between anticholinergic burden and mortality or rehospitalization in older adults discharged from hospital. METHODS:Prospective multicenter cohort study carried out with patients aged 65 and older discharged from seven acute care hospi...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,多中心研究
doi：10.1007/s00228-017-2312-5
更新日期：2017-11-01 00:00:00
abstract：PURPOSE:The aim of the study was to develop a European list of potentially inappropriate medications (PIM) for older people, which can be used for the analysis and comparison of prescribing patterns across European countries and for clinical practice. METHODS:A preliminary PIM list was developed, based on the German P...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,多中心研究
doi：10.1007/s00228-015-1860-9
更新日期：2015-07-01 00:00:00
abstract：PURPOSE:Aflibercept, a fully humanized vascular endothelial growth factor (VEGF)-targeted agent, has emerged as an effective therapy in the treatment of various solid tumors. We carried out an up-to-date meta-analysis to determine the risk of fatal adverse events (FAEs) in cancer patients treated with aflibercept. MET...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,meta分析
doi：10.1007/s00228-013-1633-2
更新日期：2014-04-01 00:00:00
abstract：PURPOSE:The aim of this study was to identify structure and language elements affecting the quality of responses from Scandinavian drug information centres (DICs). METHODS:Six different fictitious drug-related queries were sent to each of seven Scandinavian DICs. The centres were blinded for which queries were part of...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-017-2209-3
更新日期：2017-05-01 00:00:00
abstract：OBJECTIVE:CYP2D6 polymorphism of drug metabolism represents an important source of interindividual and interethnic variation in drug response. Since this polymorphism has not been studied in an Iranian population, the present study was undertaken. METHODS:Two hundred healthy unrelated Iranian subjects participated in ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-004-0859-4
更新日期：2005-02-01 00:00:00
abstract：:The effect of drinking grapefruit juice on the acute pharmacokinetic and haemodynamic actions of the dihydropyridine calcium antagonist felodipine given as a 5 mg plain tablet has been studied in nine, healthy, middle-aged males. Compared to water, grapefruit juice caused an increase in Cmax from mean 6 to 16 nmol.l-1...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00266354
更新日期：1992-01-01 00:00:00
abstract：:Nicotine chewing gum (Nicorette 4 mg) and an identical placebo gum were administered on different days, in a double-blind cross over fashion, to 4 men, aged 25-52 years, and 4 women, aged 21-49 years, all healthy non-smokers. The subjects chewed the gum for 30 min and heart rate, blood pressure, electrocardiogram, fin...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/BF00613610
更新日期：1982-10-01 00:00:00
abstract：OBJECTIVE:The efficacy, safety, tolerability and speed of onset of the hypotensive action of the combination of oral enalapril (10 mg) prazosin (1 mg) and hydrochlorothiazide (50 mg) has been assessed in 12 Nigerians with severe hypertension (Diastolic BP > or = 115 mmHg). PATIENTS:The ages of the patients ranged from...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s002280050158
更新日期：1996-01-01 00:00:00
abstract：OBJECTIVE:To assess the effect of ciprofloxacin on the pharmacokinetics of ropivacaine. METHODS. In a double-blind, randomised, cross-over study, nine healthy volunteers were treated for 2.5 days with 500 mg oral ciprofloxacin or placebo twice daily. On day 3, they received a single dose of 0.6 mg/kg ropivacaine intrav...
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/s00228-002-0540-8
更新日期：2003-02-01 00:00:00
