Abstract：
:1. The aromatic 2-hydroxylation of imipramine was studied in microsomes from three human livers. The kinetics were best described by a biphasic enzyme model. The estimated values of Vmax and Km for the high affinity site ranged from 3.2 to 5.7 nmol mg-1 h-1 and from 25 to 31 microM, respectively. 2. Quinidine was a potent inhibitor of the high affinity site for the 2-hydroxylation of imipramine in microsomes from all three human livers, with apparent Ki-values ranging from 9 to 92 nM. This finding strongly suggests that the high affinity enzyme is CYP2D6, the source of the sparteine/debrisoquine oxidation polymorphism. 3. The selective serotonin reuptake inhibitors (SSRI), paroxetine, fluoxetine and norfluoxetine were potent inhibitors of the high affinity site having apparent Ki-values of 0.36, 0.92 and 0.33 microM, respectively. Three other SSRIs, citalopram, desmethylcitalopram and fluvoxamine, were less potent inhibitors of CYP2D6, with apparent Ki-values of 19, 1.3 and 3.9 microM, respectively. 4. Among 20 drugs screened, fluvoxamine was the only potent inhibitor of the N-demethylation of imipramine, with a Ki-value of 0.14 microM. 5. Neither mephenytoin, citalopram, diazepam, omeprazole or proguanil showed any inhibition of the N-demethylation of imipramine and the role of the S-mephenytoin hydroxylase for this oxidative pathway could not be confirmed.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Skjelbo E,Brøsen Kdoi
10.1111/j.1365-2125.1992.tb04133.xkeywords:
subject
Has Abstractpub_date
1992-09-01 00:00:00pages
256-61issue
3eissn
0306-5251issn
1365-2125journal_volume
34pub_type
杂志文章abstract：:Acute myeloid leukaemia (AML) is a haematopoietic stem cell disorder, that is characterized by the clonal expansion of myeloid blasts and suppression of normal haematopoiesis. The 3 + 7 regimen is the backbone of standard first-line induction therapy among young/fit patients. However, in elderly and/or unfit patients ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bcp.14105
更新日期：2019-12-01 00:00:00
abstract：:Metabolomics is recognized as a powerful top-down system biological approach to understand genetic-environment-health paradigms paving new avenues to identify clinically relevant biomarkers. It is nowadays commonly used in clinical applications shedding new light on physiological regulatory processes of complex mammal...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1111/j.1365-2125.2012.04216.x
更新日期：2013-03-01 00:00:00
abstract：:There is concern in the UK about nonmedical use (NMU) of alprazolam (Xanax). We investigated the epidemiology of alprazolam NMU compared with diazepam using data from the Survey of Non-Medical Use of Prescription Drugs (NMURx) programme (collected 28 September-1 December 2017). The survey included 10 019 respondents a...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.13959
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abstract：:1 The effect of acebutolol, a relatively selective beta-adrenoceptor blocking drug and propranolol, a non-selective one, on the hypoglycaemic action of glibenclamide after an oral glucose load has been investigated in a group of maturity-onset diabetic patients. 2 Glibenclamide significantly reduced the blood glucose ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1982.tb01412.x
更新日期：1982-04-01 00:00:00
abstract：:1. The effects of simvastatin and pravastatin on measures of central nervous system activity were investigated in a double-blind, placebo-controlled, randomised crossover study. 2. Twenty-five healthy volunteers sequentially took 40 mg day-1 simvastatin, 40 mg day-1 pravastatin or placebo for 4 weeks, separated by a 4...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
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更新日期：1994-03-01 00:00:00
abstract：:Intravenous midazolam (mean dose of 6.3 mg) was given to 100 consecutive patients coming to endoscopy. All patients had an ear oximeter attached throughout the procedure to record continuously their levels of oxygen saturation. Eighty-five of the 100 patients had pre-endoscopy respiratory function tests measured, and ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1987.tb03104.x
更新日期：1987-06-01 00:00:00
abstract：:Adopted guidelines reflect a harmonised European approach to a specific scientific issue and should reflect the most recent scientific knowledge. However, whilst EU regulations are mandatory for all member states and EU directives must be followed by national laws in line with the directive, EMA guidelines do not have...
journal_title：British journal of clinical pharmacology
pub_type：
doi：10.1111/bcp.13883
更新日期：2019-04-01 00:00:00
abstract：AIMS:The cytochrome P450 enzyme CYP2C9 catalyses the 4'-hydroxylation of the nonsteroidal analgesic drug diclofenac in humans. We studied the influences of the known amino acid variants, CYP2C9*2 (Arg144Cys) and CYP2C9*3 (Ile359Leu), on diclofenac pharmacokinetics after a 50-mg oral dose of diclofenac in healthy volunt...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1046/j.1365-2125.2003.01712.x
更新日期：2003-01-01 00:00:00
abstract：:1. In nine patients with essential hypertension, following single and multiple doses of ketanserin, assessments were made of blood pressure and heart rate, QT interval, and pressor responses to phenylephrine and angiotensin II. 2. Significant reductions in blood pressure occurred for 6 h after the first dose, on avera...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1365-2125.1987.tb03218.x
更新日期：1987-11-01 00:00:00
abstract：AIMS:To explore the feasibility of delivering community-based drug safety testing (drug checking), to trial service design characteristics and to compare with festival-based testing. METHODS:In total, 171 substances of concern were submitted on 5 dates at 3 venues in 2 UK cities and tested using up to 6 analytical tec...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.14231
更新日期：2020-03-01 00:00:00
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journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,多中心研究,随机对照试验
doi：10.1111/bcp.13628
更新日期：2018-09-01 00:00:00
abstract：:Darunavir is an efficacious drug; however, pharmacokinetic variability has been reported. The objective of this study was to find predisposing factors for low darunavir plasma concentrations in patients starting the once- or twice-daily dosage. Darunavir plasma concentrations from January 2010 till December 2014 of hu...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.13464
更新日期：2018-03-01 00:00:00
abstract：:The kinetics of a single 0.5 mg oral dose of the triazolobenzodiazepine hypnotic triazolam, were studied in 54 healthy young men aged 20-44 years, with a mean body weight of 77 kg. Triazolam kinetics were determined from multiple plasma concentrations measured during 14 h post-dose. The overall mean +/- s.e. mean (wit...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1986.tb02951.x
更新日期：1986-12-01 00:00:00
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journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bcp.13028
更新日期：2016-10-01 00:00:00
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journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1975.tb02776.x
更新日期：1975-08-01 00:00:00
abstract：AIMS:This analysis was performed to investigate the population pharmacokinetics of clomethiazole and its effect on the natural course of sedation in acute stroke patients using a nonlinear mixed effects modelling approach. METHODS:One thousand five hundred and forty-six acute stroke patients (774 on active treatment) ...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,多中心研究,随机对照试验
doi：10.1046/j.0306-5251.2003.01850.x
更新日期：2003-08-01 00:00:00
abstract：AIMS:The study was designed to evaluate the relative bioavailability of diclofenac in plasma, subcutaneous adipose and skeletal muscle tissue after repeated topical administration using MIKA Diclofenac Spray Gel (4%), a novel formulation, and after oral dosing using VOLTAREN 50 mg enteric coated tablets. METHODS:Diclo...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
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更新日期：2005-11-01 00:00:00
abstract：:1. The purpose of this study was to evaluate possible changes in brain morphology and evoked potentials associated with daily administration of 300 mg kg-1 vigabatrin in dogs. 2. Somatosensory evoked potentials (SEP) and auditory evoked potentials (AEP) were recorded at baseline and weekly for 12 weeks of treatment an...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1989.tb03462.x
更新日期：1989-01-01 00:00:00
abstract：AIMS:The aim of the present study was to describe the real-life usage patterns of paracetamol. METHODS:The Echantillon Généraliste de Bénéficiaires (EGB) database, the permanent 1/97 representative sample from the French national healthcare insurance system, was searched in 2011 to identify usage patterns, concomitant...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.12957
更新日期：2016-08-01 00:00:00
abstract：:Children are not small adults. However, the main thesis of this review will be that children's responses to drugs have much in common with the responses in adults and indeed in other mammals. Often, it is assumed that drug effects differ in children but in reality this perception often arises because the drugs have no...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1111/j.1365-2125.2005.02445.x
更新日期：2005-06-01 00:00:00
abstract：WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT:Nitrates may facilitate syncope through various pathways, but the precise mechanism of nitrate-induced syncope is still under debate. The purpose of the present study was to compare the underlying haemodynamic mechanisms in subjects without and with presyncopal symptoms during a...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2010.03794.x
更新日期：2011-01-01 00:00:00
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journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1111/j.1365-2125.1984.tb02388.x
更新日期：1984-05-01 00:00:00
abstract：AIMS:Drug disposition in children may vary from adults due to age-related variation in drug metabolism. Microdose studies present an innovation to study pharmacokinetics (PK) in paediatrics; however, they should be used only when the PK is dose linear. We aimed to assess dose linearity of a [14 C]midazolam microdose, b...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,多中心研究
doi：10.1111/bcp.14047
更新日期：2019-10-01 00:00:00
abstract：:Alpha 1-acid glycoprotein (AAG) concentrations and propranolol binding were investigated in the serum of elderly hospitalized patients with acute illness, and healthy elderly and young subjects. Significantly greater AAG concentrations and reduced unbound propranolol fraction were observed in the elderly with acute di...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1984.tb02548.x
更新日期：1984-11-01 00:00:00
abstract：:The present study was designed to evaluate the potential anti-ischaemic activity of R 56865 in patients with coronary artery disease, scheduled to undergo percutaneous transluminal coronary angioplasty (PTCA). At baseline a complete haemodynamic profile, including cardiac output and coronary sinus blood flow (CSBF) wa...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1111/j.1365-2125.1995.tb04491.x
更新日期：1995-05-01 00:00:00
abstract：:1 A double-blind trial with parallel treatment groups was conducted to compare the safety and efficacy of mianserin with amitriptyline. 2 This was a six week trial with weekly visits. Measurements at each visit included: 21 item Hamilton Depression (HAMD) Scale. Clinical Global Impression (CGI) Scale and Treatment Eme...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1111/j.1365-2125.1983.tb05870.x
更新日期：1983-01-01 00:00:00
abstract：:Regulatory science underpins the objective evaluation of medicinal products. It is therefore imperative that regulatory science and expertise remain at the cutting edge so that innovations of ever-increasing complexity are translated safely and swiftly into effective, high-quality therapies. We undertook a comprehensi...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.14099
更新日期：2020-12-01 00:00:00
abstract：:Cefpiramide is a new parenteral cephalosporin mainly excreted in the bile. Eight patients with cholestasis and 11 healthy subjects received a single 1 g i.v. dose. Cefpiramide concentrations in plasma and urine were measured by h.p.l.c. and plasma binding was determined by ultrafiltration. Total clearance of cefpirami...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1994.tb04278.x
更新日期：1994-03-01 00:00:00
abstract：AIM:Propylene glycol (PG) is often applied as an excipient in drug formulations. As these formulations may also be used in neonates, the aim of this study was to characterize the pharmacokinetics of propylene glycol, co-administered intravenously with paracetamol (800 mg PG/1000 mg paracetamol) or phenobarbital (700 mg...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2012.04312.x
更新日期：2013-01-01 00:00:00
abstract：:Submaximal dose pentagastrin tests conducted in normal male volunteers with L-643.441, a novel histamine H2-receptor antagonist, indicate that it is a potent and long-acting inhibitor of gastric acid secretion. The effect appears dose-dependent and single doses of 50 mg are sufficient to reduce secretory potential by ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1985.tb05043.x
更新日期：1985-08-01 00:00:00
