Abstract:
:1 A method for the assay of debrisoquine 4-hydroxylase activity in vitro by microsomal fractions of human liver is described. The assay utilises gas chromatography-mass spectrometry with d9-4-hydroxydebrisoquine as internal standard. 2 The limit of detection of 4-hydroxydebrisoquine was 2 ng ml -1 and the coefficient of variation was 4.4%. 3 Debrisoquine 4-hydroxylase activity was linear with protein to concentrations above 2.1 mg ml -1 and with incubation times of at least 15 min. 4 Debrisoquine 4-hydroxylase is a microsomal enzyme with a requirement for NADPH. Activity was inhibited by carbon monoxide. It is concluded that the activity is catalysed by cytochrome P-450. 5 In three samples of human liver the mean value for Vmax of debrisoquine 4-hydroxylase activity was 69.9 +/- 14.3 pmol mg -1 min -1 and for Km it was 130 +/- 24 microM. 6 The only variable from smoking status, alcohol ingestion, sex of the patients, source of liver sample and presence of liver disease that had a significant effect on 4-hydroxylation of debrisoquine was the presence of liver disease. This was associated with a decrease in enzyme activity.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Kahn GC,Boobis AR,Murray S,Brodie MJ,Davies DSdoi
10.1111/j.1365-2125.1982.tb01430.xsubject
Has Abstractpub_date
1982-05-01 00:00:00pages
637-45issue
5eissn
0306-5251issn
1365-2125journal_volume
13pub_type
杂志文章abstract:AIMS:To investigate presence or absence of clinically relevant drug interactions (pharmacokinetic and safety/tolerability) of OBE022 with standard-of-care medicines for preterm labour, enabling coadministration and further clinical development. METHODS:Part A: open-label, randomized, 3-period crossover assessing coadm...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/bcp.13925
更新日期:2019-07-01 00:00:00
abstract:AIMS:The aim of the present study was to investigate whether differences in total and peak drug exposure upon generic substitution are due to differences between formulations or to intrasubject pharmacokinetic variability of the active substance. METHODS:The study was designed as a retrospective reanalysis of existing...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.12828
更新日期:2016-04-01 00:00:00
abstract:AIMS:Inflammation reduces hepatic clearance of many drugs with unknown therapeutic consequences. This study was carried out to examine the effect of rheumatoid arthritis (RA) on the pharmacokinetics and pharmacodynamics of verapamil. METHODS:Eight RA patients were age- and sex-matched with eight healthy volunteers. Th...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1046/j.1365-2125.2000.00314.x
更新日期:2000-12-01 00:00:00
abstract::1. The pharmacokinetics of butorphanol were evaluated in 18 female volunteers with varying degrees of renal function following a single, 1 mg transnasal dose of butorphanol tartrate. The creatinine clearance (CLCR) values for subjects in the normal (NOR), moderately impaired (MI), and severely impaired (SI) groups wer...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.1365-2125.1996.03327.x
更新日期:1996-05-01 00:00:00
abstract:AIMS:To examine the effects of salbutamol and L-arginine, two compounds acting largely on the endothelium, and the endothelium-independent agent nitroglycerin on blood pressure, arterial compliance, cardiac function and vascular resistance. METHODS:Continuous radial pulse wave analysis, whole-body impedance cardiograp...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2009.03434.x
更新日期:2009-07-01 00:00:00
abstract:AIMS:Variability in responsiveness to clopidogrel is a clinical problem in secondary prevention after cerebral ischaemia which has been suggested to be linked to competitive metabolization of clopidogrel and cytochrome P450 (CYP) 3A4-oxidated statins such as simvastatin. We assessed the hypothesis that simvastatin, in ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/bcp.12416
更新日期:2014-11-01 00:00:00
abstract::1. Labetalol, a new drug combining alpha-and beta-adrenoceptor blocking properties, has been compared with placebo in a double-blind crossover study of a group of patients with mild to moderate essential hypertension (blood pressure 150/100 to 189/114 mmHg). 2. Labetalol and propranolol lowered blood pressure satisfac...
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.1365-2125.1979.tb00898.x
更新日期:1979-01-01 00:00:00
abstract::1 The new converting enzyme inhibitor RHC 3659 was tested in 15 male volunteers. The study consisted of two parts: first, the ability of a single oral dose (5, 10, 20, 40 or 80 mg) to inhibit the pressor response to exogenous angiotensin I was tested with blood pressure and heart rate monitored continuously through an...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1981.tb01327.x
更新日期:1981-12-01 00:00:00
abstract::1. Blood and urine concentrations of the macrolide immunosuppressant FK506 and its metabolites were measured in seven orthotopic liver transplant patients after the first oral dose of FK506 (0.04 +/- 0.02 mg kg-1) used as primary immunosuppressant. A specific h.p.l.c.-MS assay was used, allowing the measurement of par...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2125.1994.tb04398.x
更新日期:1994-12-01 00:00:00
abstract:WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT:Variants in the CYP2C9 (i.e. *2 and *3) and VKORC1 (i.e. 1173C/T or -1639G/A) genes have been shown to influence warfarin dose requirements. However, these factors seem to explain less of the dose variability in African Americans who have a lower prevalence of the CYP2C9*2 and *...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2010.03709.x
更新日期:2010-09-01 00:00:00
abstract::A single oral dose of sotalol (160 mg) was administered to control subjects with normal renal function and patients with chronic renal failure in the interdialysis period to estimate the elimination kinetics of the drug. Sotalol concentrations in body fluids were measured fluorimetrically using a modified Garrett and ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1976.tb00601.x
更新日期:1976-04-01 00:00:00
abstract:AIMS:The aims of the study were to determine the effect of advice from the Scottish Medicines Consortium (SMC) on the use of medicines within Scotland's National Health Service (NHS) and generate hypotheses that may explain differences in the impact of advice on the use of individual medicines. METHODS:A retrospective...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2010.03826.x
更新日期:2011-02-01 00:00:00
abstract:AIM:We compared the efficacy of melatonin and placebo as adjuvants in the withdrawal of patients from long term temazepam, zopiclone or zolpidem (here 'BZD') use. METHODS:A double-blind, placebo-controlled, randomized trial was conducted in a primary health care outpatient clinic. Ninety-two men or women (≥55 years) w...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/bcp.12294
更新日期:2014-06-01 00:00:00
abstract:AIMS:To evaluate the electroencephalographic (EEG) effects, blood concentrations, vehicle irritation and dose-effect relationships for diazepam administered nasally. METHODS:The study had a cross-over design with eight healthy volunteers (one drop out). It consisted of four legs with four different administrations: in...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1046/j.0306-5251.2001.01486.x
更新日期:2001-11-01 00:00:00
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:AIMS:Antidepressant use has increased in the last decade. Several studies have suggested a possible association between maternal antidepressant use and teratogenic effects. METHODS:The pharmacy prescription database IADB.nl was used for a cohort study in which laxative and antidiarrhoeal medication use in children aft...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2125.2011.04081.x
更新日期:2012-01-01 00:00:00
abstract::1. A new method for perfusing a 10 cm segment of jejunum in humans has been used in seven subjects to study the effect of the amino acid L-leucine (40 mM) on the intestinal absorption of levodopa (2.5 mM). The tube contains six channels and has two inflatable balloons, which enable a perfusion of a closed and defined ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1993.tb05691.x
更新日期:1993-03-01 00:00:00
abstract:AIMS:To study the impact of risperidone (RISP) on clozapine (CLZ) biotransformation in vitro in microsomal fractions containing varying expression of CYP oxidases and in vivo in patients. METHODS:Human liver microsomes (n= 11) were assessed for expression of CYPs 1A2, 2D6 and 3A4, because these enzymes mediate RISP an...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1111/j.1365-2125.2009.03476.x
更新日期:2009-10-01 00:00:00
abstract:AIMS:To determine whether and to what extent bronchoconstriction affects plasma concentrations of fluticasone and budesonide following inhalation. METHODS:Twenty people with mild asthma inhaled 1000 microg fluticasone (Accuhaler) plus 800 microg budesonide (Turbohaler) on two visits. On one occasion, prior to drug inh...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/j.1365-2125.2007.02856.x
更新日期:2007-10-01 00:00:00
abstract:AIMS:To summarize and extend the main conclusions and recommendations relevant to drug management during acute kidney disease (AKD) as agreed at the 16th Acute Disease Quality Initiative (ADQI) consensus conference. METHODS:Using a modified Delphi method to achieve consensus, experts attending the 16th ADQI consensus ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.13449
更新日期:2018-02-01 00:00:00
abstract::When using biopsy pathology in clinical pharmacology to assess drug efficacy in the gastrointestinal tract, a number of questions must be answered: Is the biopsy necessary or more effective than macroscopic views by endoscopy? Can we extract maximal information from the specimen? Are there surrogate serum or other mar...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1046/j.1365-2125.2003.01981.x
更新日期:2003-11-01 00:00:00
abstract::1. The absorption of ciprofloxacin from different regions of the human gastrointestinal tract was investigated in four healthy males using a remote-controlled drug delivery device (hf-capsule). 2. Significant differences in AUC were observed in the control study (oral administration of ciprofloxacin solution without t...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1990.tb03740.x
更新日期:1990-07-01 00:00:00
abstract::1. The systemic effects of inhaled fluticasone propionate (FP), administered via Diskhaler, on the hypothalamo-pituitary-adrenal (HPA) axis were assessed primarily by measuring plasma cortisol at frequent intervals for 20 h after drug administration. 2. FP showed a dose-related suppression of plasma cortisol measured ...
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.1365-2125.1994.tb04393.x
更新日期:1994-12-01 00:00:00
abstract:AIM:Experimental pain models may help to evaluate the mechanisms of analgesics and target the clinical indications for their use. This review, the second in a series of two, addresses how the efficacy of non-opioid analgesics have been assessed in human volunteers using experimental pain models. METHODS:A literature s...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2125.2009.03433.x
更新日期:2009-09-01 00:00:00
abstract:AIMS:Pupillography is a noninvasive and cost-effective method to determine autonomic nerve activity. Genetic variants in cytochrome P450 (CYP), dopamine receptor (DRD2, DRD3), serotonin receptor (HTR2A, HTR2C) and ATP-binding cassette subfamily B (ABCB1) genes, among others, were previously associated with the pharmaco...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14300
更新日期:2020-10-01 00:00:00
abstract:AIM:Characterization of the biliary disposition of GSK1325756, using a non-invasive bile sampling technique and spectrometric analyses, to inform the major routes of metabolic elimination and to enable an assessment of victim drug interaction risk. METHOD:Sixteen healthy, elderly subjects underwent non-invasive bile c...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2012.04352.x
更新日期:2013-02-01 00:00:00
abstract::1 Seventeen men, aged 45-57 yr, with essential hypertension showed obvious and, in the standing position, dose-related reductions in blood pressure during treatment with oral labetalol with weekly dose increments. 2 Pulse rate changes were not related to dose but reduced compared with pre-treatment values. 3 No postur...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:
更新日期:1976-08-01 00:00:00
abstract::We define a me-too drug as a pharmacologically active compound that is structurally related to a first-in-class compound, regarded as belonging to the same therapeutic class as the original compound, and used for the same therapeutic purposes, but which may differ in some respects, such as specificity of pharmacologic...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bcp.14327
更新日期:2020-11-01 00:00:00
abstract::We have measured the psychological effects of acebutolol and atenolol in sixteen patients with essential hypertension. The drugs were administered in a randomized, placebo-controlled, double-blind manner, in single daily doses of 100 mg atenolol, 400 mg acebutolol or placebo for periods of 6 weeks, each drug period be...
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.1365-2125.1984.tb02356.x
更新日期:1984-03-01 00:00:00
abstract:AIMS:To develop a polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP)-based assay to genotype for hepatic CYP3A5 expression and to use this assay to study a British population. METHODS:CYP3A5-specific primers were designed with one including a base-pair mismatch to create a RsaI site in sam...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.1365-2125.2003.01798.x
更新日期:2003-06-01 00:00:00